Variant 11-46680520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004308.5(ARHGAP1):c.787C>T(p.Leu263Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00826 in 1,614,122 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 83 hom. )

Consequence

ARHGAP1
NM_004308.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

ARHGAP1 (HGNC:673): (Rho GTPase activating protein 1) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein contains a SRC homology 3 domain and interacts with Bcl-2-associated protein family members. [provided by RefSeq, Aug 2012]

ARHGAP1 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=0.010460794).

BP6

Variant 11-46680520-G-A is Benign according to our data. Variant chr11-46680520-G-A is described in ClinVar as [Benign]. Clinvar id is 711378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00633 (964/152320) while in subpopulation SAS AF= 0.022 (106/4828). AF 95% confidence interval is 0.0186. There are 7 homozygotes in gnomad4. There are 493 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARHGAP1	NM_004308.5 linkuse as main transcript	c.787C>T	p.Leu263Phe	missense_variant	9/13	ENST00000311956.9	NP_004299.1
ARHGAP1	XM_047426933.1 linkuse as main transcript	c.787C>T	p.Leu263Phe	missense_variant	9/13		XP_047282889.1
ARHGAP1	XM_024448520.2 linkuse as main transcript	c.655C>T	p.Leu219Phe	missense_variant	8/12		XP_024304288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARHGAP1	ENST00000311956.9 linkuse as main transcript	c.787C>T	p.Leu263Phe	missense_variant	9/13	1	NM_004308.5	ENSP00000310491	P1
ARHGAP1	ENST00000526423.1 linkuse as main transcript	n.475C>T		non_coding_transcript_exon_variant	4/8	1
ARHGAP1	ENST00000528837.5 linkuse as main transcript	c.649C>T	p.Leu217Phe	missense_variant	7/11	5		ENSP00000434883

Frequencies

GnomAD3 genomes

AF:

0.00634

AC:

965

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00926

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00765

AC:

1923

AN:

251272

Hom.:

AF XY:

0.00877

AC XY:

1191

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00755

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0217

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00846

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00846

AC:

12372

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00888

AC XY:

6455

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.00727

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00849

Gnomad4 OTH exome

AF:

0.00841

GnomAD4 genome

AF:

0.00633

AC:

964

AN:

152320

Hom.:

Cov.:

AF XY:

0.00662

AC XY:

493

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0220

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00926

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.00642

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0104

AC:

ExAC

AF:

0.00749

AC:

909

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00984

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

-0.019

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.99

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.3

REVEL

Benign

0.23

Sift

Uncertain

0.014

Sift4G

Benign

0.13

Polyphen

0.94

Vest4

0.59

MVP

0.37

MPC

0.73

ClinPred

0.045

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.34

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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