Variant 19-19634670-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000203556.9(GMIP):c.1921G>A(p.Asp641Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,611,504 control chromosomes in the GnomAD database, including 1,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 91 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1007 hom. )

Consequence

GMIP
ENST00000203556.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

GMIP (HGNC:24852): (GEM interacting protein) This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

GMIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031639338).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0268 (4069/152032) while in subpopulation NFE AF= 0.0363 (2466/67964). AF 95% confidence interval is 0.0351. There are 91 homozygotes in gnomad4. There are 2000 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMIP	NM_016573.4 linkuse as main transcript	c.1921G>A	p.Asp641Asn	missense_variant	18/21	ENST00000203556.9	NP_057657.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMIP	ENST00000203556.9 linkuse as main transcript	c.1921G>A	p.Asp641Asn	missense_variant	18/21	1	NM_016573.4	ENSP00000203556	P1	Q9P107-1
GMIP	ENST00000587238.5 linkuse as main transcript	c.1843G>A	p.Asp615Asn	missense_variant	17/20	1		ENSP00000467054		Q9P107-2
GMIP	ENST00000586269.1 linkuse as main transcript	n.453+122G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4070

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00610

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0718

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0654

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0363

Gnomad OTH

AF:

0.0221

GnomAD3 exomes

AF:

0.0298

AC:

7454

AN:

249804

Hom.:

150

AF XY:

0.0307

AC XY:

4140

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.00512

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.0621

Gnomad EAS exome

AF:

0.000382

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.0634

Gnomad NFE exome

AF:

0.0368

Gnomad OTH exome

AF:

0.0347

GnomAD4 exome

AF:

0.0352

AC:

51387

AN:

1459472

Hom.:

1007

Cov.:

AF XY:

0.0350

AC XY:

25373

AN XY:

725758

show subpopulations

Gnomad4 AFR exome

AF:

0.00617

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0628

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0173

Gnomad4 FIN exome

AF:

0.0613

Gnomad4 NFE exome

AF:

0.0378

Gnomad4 OTH exome

AF:

0.0320

GnomAD4 genome

AF:

0.0268

AC:

4069

AN:

152032

Hom.:

Cov.:

AF XY:

0.0269

AC XY:

2000

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00608

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0718

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0654

Gnomad4 NFE

AF:

0.0363

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0333

Hom.:

203

Bravo

AF:

0.0225

TwinsUK

AF:

0.0423

AC:

157

ALSPAC

AF:

0.0358

AC:

138

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.0350

AC:

301

ExAC

AF:

0.0287

AC:

3482

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0346

EpiControl

AF:

0.0330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.81

T;D

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

N;.

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

1.3

N;.

REVEL

Benign

0.066

Sift

Benign

0.77

T;.

Sift4G

Benign

0.66

T;T

Polyphen

0.038

B;.

Vest4

0.056

MPC

0.28

ClinPred

0.0027

GERP RS

2.5

Varity_R

0.066

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over