NM_001023570.4:c.1178T>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001023570.4(IQCB1):c.1178T>A(p.Ile393Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,613,104 control chromosomes in the GnomAD database, including 12,634 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 813 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11821 hom. )

Consequence

IQCB1
NM_001023570.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: 1.34

Publications

37 publications found

Variant links:

Genes affected

IQCB1 (HGNC:28949): (IQ motif containing B1) This gene encodes a nephrocystin protein that interacts with calmodulin and the retinitis pigmentosa GTPase regulator protein. The encoded protein has a central coiled-coil region and two calmodulin-binding IQ domains. It is localized to the primary cilia of renal epithelial cells and connecting cilia of photoreceptor cells. The protein is thought to play a role in ciliary function. Defects in this gene result in Senior-Loken syndrome type 5. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Jan 2016]

IQCB1 Gene-Disease associations (from GenCC):

Senior-Loken syndrome 5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IQCB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002072066).

BP6

Variant 3-121788384-A-T is Benign according to our data. Variant chr3-121788384-A-T is described in ClinVar as Benign. ClinVar VariationId is 167196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4 link	c.1178T>A	p.Ile393Asn	missense_variant	Exon 12 of 15	ENST00000310864.11	NP_001018864.2	Q15051-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IQCB1	ENST00000310864.11 link	c.1178T>A	p.Ile393Asn	missense_variant	Exon 12 of 15	1	NM_001023570.4	ENSP00000311505.6	Q15051-1
IQCB1	ENST00000349820.10 link	c.779T>A	p.Ile260Asn	missense_variant	Exon 9 of 12	1		ENSP00000323756.7	Q15051-2
IQCB1	ENST00000393650.7 link	n.*156T>A		non_coding_transcript_exon_variant	Exon 11 of 14	5		ENSP00000377261.3	Q15051-3
IQCB1	ENST00000393650.7 link	n.*156T>A		3_prime_UTR_variant	Exon 11 of 14	5		ENSP00000377261.3	Q15051-3

Frequencies

GnomAD3 genomes

AF:

0.0894

AC:

13593

AN:

152082

Hom.:

813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.0633

Gnomad ASJ

AF:

0.0980

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.0925

GnomAD2 exomes

AF:

0.0914

AC:

22980

AN:

251436

AF XY:

0.0914

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0561

Gnomad ASJ exome

AF:

0.0910

Gnomad EAS exome

AF:

0.00272

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.0934

GnomAD4 exome

AF:

0.120

AC:

174882

AN:

1460904

Hom.:

11821

Cov.:

AF XY:

0.117

AC XY:

84776

AN XY:

726770

show subpopulations

African (AFR)

AF:

0.0295

AC:

987

AN:

33466

American (AMR)

AF:

0.0584

AC:

2610

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0854

AC:

2231

AN:

26126

East Asian (EAS)

AF:

0.00184

AC:

AN:

39674

South Asian (SAS)

AF:

0.0295

AC:

2547

AN:

86242

European-Finnish (FIN)

AF:

0.117

AC:

6266

AN:

53370

Middle Eastern (MID)

AF:

0.0553

AC:

319

AN:

5764

European-Non Finnish (NFE)

AF:

0.138

AC:

153698

AN:

1111180

Other (OTH)

AF:

0.102

AC:

6151

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

7520

15039

22559

30078

37598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5374

10748

16122

21496

26870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0893

AC:

13591

AN:

152200

Hom.:

813

Cov.:

AF XY:

0.0856

AC XY:

6367

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0354

AC:

1472

AN:

41556

American (AMR)

AF:

0.0631

AC:

966

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0980

AC:

340

AN:

3468

East Asian (EAS)

AF:

0.00193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0261

AC:

126

AN:

4828

European-Finnish (FIN)

AF:

0.119

AC:

1254

AN:

10564

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8982

AN:

67994

Other (OTH)

AF:

0.0911

AC:

192

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

593

1186

1779

2372

2965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.118

Hom.:

349

Bravo

AF:

0.0868

TwinsUK

AF:

0.149

AC:

551

ALSPAC

AF:

0.134

AC:

515

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.130

AC:

1118

ExAC

AF:

0.0931

AC:

11300

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 28, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Senior-Loken syndrome 5

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jan 18, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22183348) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nephronophthisis

Benign:1Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.

Eigen

Benign

-0.042

Eigen_PC

Benign

0.020

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.91

D;D

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.

PhyloP100

1.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.021

Sift

Benign

0.064

T;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.81

P;P

Vest4

0.26

MPC

0.46

ClinPred

0.022

GERP RS

2.2

Varity_R

0.29

gMVP

0.34

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over