rs17849995

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.1301G>A(p.Cys434Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.256 in 1,612,350 control chromosomes in the GnomAD database, including 57,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5650 hom., cov: 31)

Exomes 𝑓: 0.26 ( 51526 hom. )

Consequence

IQCB1
NM_001023570.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.90

Publications

35 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=0.0013995767).

BP6

Variant 3-121781852-C-T is Benign according to our data. Variant chr3-121781852-C-T is described in ClinVar as Benign. ClinVar VariationId is 257090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4 link	c.1301G>A	p.Cys434Tyr	missense_variant	Exon 13 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.1301G>A	p.Cys434Tyr	missense_variant	Exon 13 of 15	1	NM_001023570.4	ENSP00000311505.6	Q15051-1
IQCB1	ENST00000349820.10 link	c.902G>A	p.Cys301Tyr	missense_variant	Exon 10 of 12	1		ENSP00000323756.7	Q15051-2
IQCB1	ENST00000393650.7 link	n.*279G>A		non_coding_transcript_exon_variant	Exon 12 of 14	5		ENSP00000377261.3	Q15051-3
IQCB1	ENST00000393650.7 link	n.*279G>A		3_prime_UTR_variant	Exon 12 of 14	5		ENSP00000377261.3	Q15051-3

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39381

AN:

151780

Hom.:

5635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.269

GnomAD2 exomes

AF:

0.300

AC:

75379

AN:

251354

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.248

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.256

AC:

373186

AN:

1460450

Hom.:

51526

Cov.:

AF XY:

0.258

AC XY:

187809

AN XY:

726566

show subpopulations

African (AFR)

AF:

0.229

AC:

7669

AN:

33452

American (AMR)

AF:

0.556

AC:

24852

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

5965

AN:

26110

East Asian (EAS)

AF:

0.160

AC:

6331

AN:

39636

South Asian (SAS)

AF:

0.389

AC:

33529

AN:

86226

European-Finnish (FIN)

AF:

0.246

AC:

13141

AN:

53336

Middle Eastern (MID)

AF:

0.236

AC:

1359

AN:

5762

European-Non Finnish (NFE)

AF:

0.239

AC:

264984

AN:

1110910

Other (OTH)

AF:

0.255

AC:

15356

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

13766

27533

41299

55066

68832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9272

18544

27816

37088

46360

<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:

0.260

AC:

39429

AN:

151900

Hom.:

5650

Cov.:

AF XY:

0.268

AC XY:

19887

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.235

AC:

9742

AN:

41432

American (AMR)

AF:

0.431

AC:

6573

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

748

AN:

3466

East Asian (EAS)

AF:

0.167

AC:

864

AN:

5170

South Asian (SAS)

AF:

0.405

AC:

1943

AN:

4796

European-Finnish (FIN)

AF:

0.248

AC:

2609

AN:

10540

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16129

AN:

67944

Other (OTH)

AF:

0.266

AC:

561

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1425

2850

4274

5699

7124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.248

Hom.:

9221

Bravo

AF:

0.268

TwinsUK

AF:

0.248

AC:

920

ALSPAC

AF:

0.250

AC:

963

ESP6500AA

AF:

0.233

AC:

1026

ESP6500EA

AF:

0.239

AC:

2057

ExAC

AF:

0.289

AC:

35062

Asia WGS

AF:

0.313

AC:

1088

AN:

3478

EpiCase

AF:

0.242

EpiControl

AF:

0.238

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Senior-Loken syndrome 5

Benign:3

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephronophthisis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

M;.

PhyloP100

3.9

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.20

Sift

Benign

0.16

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.83

P;D

Vest4

0.24

MPC

0.40

ClinPred

0.025

GERP RS

3.7

Varity_R

0.12

gMVP

0.40

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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