Variant chr15-90449581-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003870.4(IQGAP1):c.1100A>G(p.Gln367Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,460,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

IQGAP1
NM_003870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.082220465).

BS2

High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IQGAP1	NM_003870.4 link	c.1100A>G	p.Gln367Arg	missense_variant	11/38	ENST00000268182.10	NP_003861.1	P46940A0A024RC65
IQGAP1	XM_047433204.1 link	c.1100A>G	p.Gln367Arg	missense_variant	11/30		XP_047289160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IQGAP1	ENST00000268182.10 link	c.1100A>G	p.Gln367Arg	missense_variant	11/38	1	NM_003870.4	ENSP00000268182.5	P46940
IQGAP1	ENST00000560738.1 link	c.107-16466A>G		intron_variant		5		ENSP00000453181.1	H0YLE8
IQGAP1	ENST00000633485.1 link	n.1100A>G		non_coding_transcript_exon_variant	11/39	5		ENSP00000488618.1	A0A0J9YXZ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000100

AC:

AN:

248904

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

134414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000728

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1460722

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000740

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000906

AC:

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

Jan 26, 2022

The c.1100A>G (p.Q367R) alteration is located in exon 11 (coding exon 11) of the IQGAP1 gene. This alteration results from a A to G substitution at nucleotide position 1100, causing the glutamine (Q) at amino acid position 367 to be replaced by an arginine (R). 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

0.080

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Benign

-0.081

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

M_CAP

Benign

0.0052

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.0

REVEL

Benign

0.14

Sift

Benign

0.35

Sift4G

Benign

0.23

Polyphen

0.0010

Vest4

0.42

MutPred

0.15

Gain of MoRF binding (P = 0.1623);

MVP

0.71

MPC

0.13

ClinPred

0.090

GERP RS

5.0

Varity_R

0.11

gMVP

0.31

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