Variant chr17-8315431-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_173728.4(ARHGEF15):c.1278G>A(p.Val426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,613,932 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 33 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.814

Variant links:

Genes affected

ARHGEF15 (HGNC:15590): (Rho guanine nucleotide exchange factor 15) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. This gene encodes a protein that functions as a specific guanine nucleotide exchange factor for RhoA. It also interacts with ephrin A4 in vascular smooth muscle cells. Two alternatively spliced transcripts variants that encode the same protein have been found for this gene. [provided by RefSeq, Aug 2010]

ARHGEF15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-8315431-G-A is Benign according to our data. Variant chr17-8315431-G-A is described in ClinVar as [Benign]. Clinvar id is 412677.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.814 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1881/152170) while in subpopulation AFR AF= 0.0421 (1745/41486). AF 95% confidence interval is 0.0404. There are 39 homozygotes in gnomad4. There are 894 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF15	NM_173728.4 linkuse as main transcript	c.1278G>A	p.Val426=	synonymous_variant	7/16	ENST00000361926.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ARHGEF15	ENST00000361926.8 linkuse as main transcript	c.1278G>A	p.Val426=	synonymous_variant	7/16	1	NM_173728.4	P1
ARHGEF15	ENST00000421050.2 linkuse as main transcript	c.1278G>A	p.Val426=	synonymous_variant	7/16	1		P1
ARHGEF15	ENST00000647883.1 linkuse as main transcript	c.741G>A	p.Val247=	synonymous_variant	4/13
ARHGEF15	ENST00000578286.1 linkuse as main transcript	n.326G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1884

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00326

AC:

820

AN:

251166

Hom.:

AF XY:

0.00251

AC XY:

341

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00120

AC:

1756

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

756

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0418

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.0124

AC:

1881

AN:

152170

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

894

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0421

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00639

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.2

DANN

Benign

0.80

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