Variant 15-90452925-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_003870.4(IQGAP1):c.1313G>A(p.Arg438Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000083 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

IQGAP1
NM_003870.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.07

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=0.08394432).

BP6

Variant 15-90452925-G-A is Benign according to our data. Variant chr15-90452925-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2354948.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQGAP1	NM_003870.4 linkuse as main transcript	c.1313G>A	p.Arg438Gln	missense_variant	12/38	ENST00000268182.10
IQGAP1	XM_047433204.1 linkuse as main transcript	c.1313G>A	p.Arg438Gln	missense_variant	12/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IQGAP1	ENST00000268182.10 linkuse as main transcript	c.1313G>A	p.Arg438Gln	missense_variant	12/38	1	NM_003870.4	P1
IQGAP1	ENST00000560738.1 linkuse as main transcript	c.107-13122G>A		intron_variant		5
IQGAP1	ENST00000633485.1 linkuse as main transcript	c.1313G>A	p.Arg438Gln	missense_variant, NMD_transcript_variant	12/39	5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250758

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000794

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461566

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.12

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.48

M_CAP

Benign

0.0093

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.49

REVEL

Benign

0.085

Sift

Benign

0.81

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.27

MVP

0.24

MPC

0.14

ClinPred

0.049

GERP RS

2.6

Varity_R

0.028

gMVP

0.044

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