Variant chr15-32624202-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000361627.8(ARHGAP11A):c.327A>G(p.Leu109Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,612,284 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0022 ( 4 hom. )

Consequence

ARHGAP11A
ENST00000361627.8 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.134

Variant links:

Genes affected

ARHGAP11A (HGNC:15783): (Rho GTPase activating protein 11A) This gene encodes a member of the Rho GTPase activating protein family. In response to DNA damage, the encoded protein interacts with the p53 tumor suppressor protein and stimulates its tetramerization, which results in cell-cycle arrest and apoptosis. A chromosomal deletion that includes this gene is one cause of Prader-Willi syndrome, and an intronic variant of this gene may be associated with sleep duration in children. This gene is highly expressed in colon cancers and in a human basal-like breast cancer cell line. This gene also produces a ARHGAP11A-SCG5 readthrough transcript and ARHGAP11A-SCG5 protein. [provided by RefSeq, Feb 2019]

ARHGAP11A links:

ARHGAP11A-SCG5 (HGNC:56310): (ARHGAP11A-SCG5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ARHGAP11A (Rho GTPase activating protein 11A) and SCG5 (secretogranin V) genes on chromosome 15q13.3. The readthrough transcript encodes a fusion protein that shares sequence identity with both the ARHGAP11A and SCG5 gene products. [provided by RefSeq, Feb 2019]

ARHGAP11A-SCG5 links:

ENSG00000285948 (HGNC:):

ENSG00000285948 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 15-32624202-A-G is Benign according to our data. Variant chr15-32624202-A-G is described in ClinVar as [Benign]. Clinvar id is 713581.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.134 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP11A	NM_014783.6 linkuse as main transcript	c.327A>G	p.Leu109Leu	synonymous_variant	4/12	ENST00000361627.8	NP_055598.1	Q6P4F7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP11A	ENST00000361627.8 linkuse as main transcript	c.327A>G	p.Leu109Leu	synonymous_variant	4/12	1	NM_014783.6	ENSP00000355090.3		Q6P4F7-1
ARHGAP11A-SCG5	ENST00000692248.1 linkuse as main transcript	c.327A>G	p.Leu109Leu	synonymous_variant	4/14			ENSP00000510771.1		A0A8I5KWH8

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

194

AN:

151270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000581

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000968

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.00113

AC:

278

AN:

246808

Hom.:

AF XY:

0.00122

AC XY:

164

AN XY:

133990

show subpopulations

Gnomad AFR exome

AF:

0.000711

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.000298

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00207

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00221

AC:

3235

AN:

1460910

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1562

AN XY:

726780

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00273

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00128

AC:

194

AN:

151374

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

73888

show subpopulations

Gnomad4 AFR

AF:

0.000580

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000971

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00124

EpiCase

AF:

0.00256

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.6

DANN

Benign

0.65

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