Variant chr11-46679666-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000311956.9(ARHGAP1):c.1009C>T(p.His337Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,738 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ARHGAP1
ENST00000311956.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

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:

ARHGAP1 (HGNC:):

ARHGAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18821695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP1	NM_004308.5 linkuse as main transcript	c.1009C>T	p.His337Tyr	missense_variant	11/13	ENST00000311956.9	NP_004299.1	Q07960
ARHGAP1	XM_047426933.1 linkuse as main transcript	c.1009C>T	p.His337Tyr	missense_variant	11/13		XP_047282889.1
ARHGAP1	XM_024448520.2 linkuse as main transcript	c.877C>T	p.His293Tyr	missense_variant	10/12		XP_024304288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGAP1	ENST00000311956.9 linkuse as main transcript	c.1009C>T	p.His337Tyr	missense_variant	11/13	1	NM_004308.5	ENSP00000310491.4	Q07960
ARHGAP1	ENST00000526423.1 linkuse as main transcript	n.752C>T		non_coding_transcript_exon_variant	6/8	1
ARHGAP1	ENST00000528837.5 linkuse as main transcript	c.868C>T	p.His290Tyr	missense_variant	9/11	5		ENSP00000434883.1	H0YE29

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 07, 2022

The c.1009C>T (p.H337Y) alteration is located in exon 11 (coding exon 10) of the ARHGAP1 gene. This alteration results from a C to T substitution at nucleotide position 1009, causing the histidine (H) at amino acid position 337 to be replaced by a tyrosine (Y). 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

0.084

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.14

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.83

M_CAP

Benign

0.0052

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.83

MutationTaster

Benign

0.84

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.3

REVEL

Benign

0.087

Sift

Benign

0.32

Sift4G

Benign

0.14

Polyphen

0.033

Vest4

0.29

MutPred

0.54

Loss of helix (P = 0.3949);

MVP

0.30

MPC

0.33

ClinPred

0.63

GERP RS

4.4

Varity_R

0.26

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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