rs4543051

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001023570.4(IQCB1):c.574C>T(p.Leu192Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,508,050 control chromosomes in the GnomAD database, including 298,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31860 hom., cov: 30)

Exomes 𝑓: 0.62 ( 266668 hom. )

Consequence

IQCB1
NM_001023570.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.76

Publications

29 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-121807357-G-A is Benign according to our data. Variant chr3-121807357-G-A is described in ClinVar as Benign. ClinVar VariationId is 198444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IQCB1	NM_001023570.4 link	c.574C>T	p.Leu192Leu	synonymous_variant	Exon 7 of 15	ENST00000310864.11	NP_001018864.2	Q15051-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11 link	c.574C>T	p.Leu192Leu	synonymous_variant	Exon 7 of 15	1	NM_001023570.4	ENSP00000311505.6		Q15051-1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97432

AN:

151396

Hom.:

31828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.663

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.629

GnomAD2 exomes

AF:

0.628

AC:

157351

AN:

250652

AF XY:

0.622

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.747

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.622

AC:

843637

AN:

1356536

Hom.:

266668

Cov.:

AF XY:

0.621

AC XY:

423064

AN XY:

680730

show subpopulations

African (AFR)

AF:

0.710

AC:

22232

AN:

31306

American (AMR)

AF:

0.738

AC:

32814

AN:

44444

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

14091

AN:

25364

East Asian (EAS)

AF:

0.299

AC:

11675

AN:

39092

South Asian (SAS)

AF:

0.655

AC:

55095

AN:

84126

European-Finnish (FIN)

AF:

0.666

AC:

35455

AN:

53256

Middle Eastern (MID)

AF:

0.539

AC:

2994

AN:

5556

European-Non Finnish (NFE)

AF:

0.625

AC:

634973

AN:

1016632

Other (OTH)

AF:

0.604

AC:

34308

AN:

56760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

13004

26008

39012

52016

65020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16374

32748

49122

65496

81870

<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:

0.644

AC:

97515

AN:

151514

Hom.:

31860

Cov.:

AF XY:

0.645

AC XY:

47722

AN XY:

74024

show subpopulations

African (AFR)

AF:

0.715

AC:

29577

AN:

41388

American (AMR)

AF:

0.665

AC:

10117

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1917

AN:

3462

East Asian (EAS)

AF:

0.312

AC:

1610

AN:

5164

South Asian (SAS)

AF:

0.658

AC:

3169

AN:

4814

European-Finnish (FIN)

AF:

0.663

AC:

6941

AN:

10468

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.622

AC:

42079

AN:

67690

Other (OTH)

AF:

0.628

AC:

1324

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1694

3388

5081

6775

8469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.632

Hom.:

13377

Bravo

AF:

0.641

Asia WGS

AF:

0.563

AC:

1932

AN:

3424

EpiCase

AF:

0.610

EpiControl

AF:

0.603

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 06, 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

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Senior-Loken syndrome 5

Benign:2

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

- -

May 22, 2019

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.4

(source)

DANN

Benign

0.65

PhyloP100

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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