3-121808979-A-G

Position:

chr3-121808979-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001023570.4(IQCB1):c.424T>C(p.Phe142Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00187 in 1,608,856 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

IQCB1
NM_001023570.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.26

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=0.006232977).

BP6

Variant 3-121808979-A-G is Benign according to our data. Variant chr3-121808979-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 219982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-121808979-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1557/152020) while in subpopulation AFR AF= 0.035 (1454/41564). AF 95% confidence interval is 0.0335. There are 19 homozygotes in gnomad4. There are 693 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQCB1	NM_001023570.4 linkuse as main transcript	c.424T>C	p.Phe142Leu	missense_variant	6/15	ENST00000310864.11	NP_001018864.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IQCB1	ENST00000310864.11 linkuse as main transcript	c.424T>C	p.Phe142Leu	missense_variant	6/15	1	NM_001023570.4	ENSP00000311505	P1	Q15051-1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1554

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000885

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00269

AC:

675

AN:

250804

Hom.:

AF XY:

0.00206

AC XY:

279

AN XY:

135608

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.00100

AC:

1458

AN:

1456836

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

626

AN XY:

724998

show subpopulations

Gnomad4 AFR exome

AF:

0.0369

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000208

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.0102

AC:

1557

AN:

152020

Hom.:

Cov.:

AF XY:

0.00932

AC XY:

693

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0350

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000885

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0390

AC:

172

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00320

AC:

389

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 14, 2021	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Senior-Loken syndrome 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.92

P;D

Vest4

0.84

MutPred

0.24

Loss of loop (P = 0.0153);Loss of loop (P = 0.0153);

MVP

0.57

MPC

0.34

ClinPred

0.048

GERP RS

5.5

Varity_R

0.34

gMVP

0.60

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

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