Variant 15-90390776-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003870.4(IQGAP1):c.58G>A(p.Val20Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,601,682 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 2 hom. )

Consequence

IQGAP1
NM_003870.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

IQGAP1 (HGNC:6110): (IQ motif containing GTPase activating protein 1) This gene encodes a member of the IQGAP family. The protein contains four IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. It interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. Expression of the protein is upregulated by gene amplification in two gastric cancer cell lines. [provided by RefSeq, Jul 2008]

IQGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023983091).

BS2

High AC in GnomAd at 102 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP1	NM_003870.4 linkuse as main transcript	c.58G>A	p.Val20Ile	missense_variant, splice_region_variant	2/38	ENST00000268182.10
IQGAP1	XM_047433204.1 linkuse as main transcript	c.58G>A	p.Val20Ile	missense_variant, splice_region_variant	2/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQGAP1	ENST00000268182.10 linkuse as main transcript	c.58G>A	p.Val20Ile	missense_variant, splice_region_variant	2/38	1	NM_003870.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000431

AC:

108

AN:

250398

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000710

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000791

AC:

1146

AN:

1449414

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

546

AN XY:

721792

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000582

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000976

Gnomad4 OTH exome

AF:

0.000634

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152268

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000793

Hom.:

Bravo

AF:

0.000631

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.58G>A (p.V20I) alteration is located in exon 2 (coding exon 2) of the IQGAP1 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the valine (V) at amino acid position 20 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.050

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.024

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-0.23

N;.

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.067

Sift

Benign

0.77

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0070

B;.

Vest4

0.16

MVP

0.19

MPC

0.10

ClinPred

0.047

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.10

gMVP

0.092

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