rs4543051

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001023570.4(IQCB1):c.574C>T(p.Leu192=) 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:8

Conservation

PhyloP100: 1.76

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 198444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121807357-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
IQCB1	NM_001023570.4 linkuse as main transcript	c.574C>T	p.Leu192=	synonymous_variant	7/15	ENST00000310864.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCB1	ENST00000310864.11 linkuse as main transcript	c.574C>T	p.Leu192=	synonymous_variant	7/15	1	NM_001023570.4	P1	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

GnomAD3 exomes

AF:

0.628

AC:

157351

AN:

250652

Hom.:

50825

AF XY:

0.622

AC XY:

84289

AN XY:

135460

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 SAS exome

AF:

0.662

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

Gnomad4 AFR exome

AF:

0.710

Gnomad4 AMR exome

AF:

0.738

Gnomad4 ASJ exome

AF:

0.556

Gnomad4 EAS exome

AF:

0.299

Gnomad4 SAS exome

AF:

0.655

Gnomad4 FIN exome

AF:

0.666

Gnomad4 NFE exome

AF:

0.625

Gnomad4 OTH exome

AF:

0.604

GnomAD4 genome

AF:

0.644

AC:

97515

AN:

151514

Hom.:

31860

Cov.:

AF XY:

0.645

AC XY:

47722

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.715

Gnomad4 AMR

AF:

0.665

Gnomad4 ASJ

AF:

0.554

Gnomad4 EAS

AF:

0.312

Gnomad4 SAS

AF:

0.658

Gnomad4 FIN

AF:

0.663

Gnomad4 NFE

AF:

0.622

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.631

Hom.:

13178

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:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 06, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Senior-Loken syndrome 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.4

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over