3-121788384-A-T

Position:

chr3-121788384-A-T

Variant summary

Our verdict is Benign. Variant got -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. 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:9O:1

Conservation

PhyloP100: 1.34

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 -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 id is 167196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121788384-A-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
IQCB1	NM_001023570.4 linkuse as main transcript	c.1178T>A	p.Ile393Asn	missense_variant	12/15	ENST00000310864.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCB1	ENST00000310864.11 linkuse as main transcript	c.1178T>A	p.Ile393Asn	missense_variant	12/15	1	NM_001023570.4	P1	Q15051-1
IQCB1	ENST00000349820.10 linkuse as main transcript	c.779T>A	p.Ile260Asn	missense_variant	9/12	1			Q15051-2
IQCB1	ENST00000393650.7 linkuse as main transcript	c.*156T>A		3_prime_UTR_variant, NMD_transcript_variant	11/14	5			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

GnomAD3 exomes

AF:

0.0914

AC:

22980

AN:

251436

Hom.:

1424

AF XY:

0.0914

AC XY:

12416

AN XY:

135888

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 SAS exome

AF:

0.0269

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

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.0584

Gnomad4 ASJ exome

AF:

0.0854

Gnomad4 EAS exome

AF:

0.00184

Gnomad4 SAS exome

AF:

0.0295

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0893

AC:

13591

AN:

152200

Hom.:

813

Cov.:

AF XY:

0.0856

AC XY:

6367

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.0631

Gnomad4 ASJ

AF:

0.0980

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0261

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.0911

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:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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)	Apr 28, 2014	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 22183348) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nephronophthisis

Benign:1Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Senior-Loken syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

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

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;.

MutationTaster

Benign

0.99

P;P

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

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