Variant 17-8312609-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_173728.4(ARHGEF15):c.570C>T(p.Thr190Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,613,026 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 30)

Exomes 𝑓: 0.015 ( 191 hom. )

Consequence

ARHGEF15
NM_173728.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.95

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:

ARHGEF15 (HGNC:):

ARHGEF15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 17-8312609-C-T is Benign according to our data. Variant chr17-8312609-C-T is described in ClinVar as [Benign]. Clinvar id is 412675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8312609-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.95 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0124 (1895/152276) while in subpopulation NFE AF= 0.0171 (1166/68010). AF 95% confidence interval is 0.0163. There are 20 homozygotes in gnomad4. There are 926 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF15	NM_173728.4 linkuse as main transcript	c.570C>T	p.Thr190Thr	synonymous_variant	2/16	ENST00000361926.8	NP_776089.2	O94989A0A0S2Z547

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGEF15	ENST00000361926.8 linkuse as main transcript	c.570C>T	p.Thr190Thr	synonymous_variant	2/16	1	NM_173728.4	ENSP00000355026.3	O94989
ARHGEF15	ENST00000421050.2 linkuse as main transcript	c.570C>T	p.Thr190Thr	synonymous_variant	2/16	1		ENSP00000412505.1	O94989
ARHGEF15	ENST00000579439.5 linkuse as main transcript	c.570C>T	p.Thr190Thr	synonymous_variant	2/3	5		ENSP00000464540.1	J3QS60
ARHGEF15	ENST00000455564.3 linkuse as main transcript	n.683C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1897

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.0125

AC:

3093

AN:

247366

Hom.:

AF XY:

0.0124

AC XY:

1670

AN XY:

134426

show subpopulations

Gnomad AFR exome

AF:

0.00332

Gnomad AMR exome

AF:

0.00991

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0148

AC:

21660

AN:

1460750

Hom.:

191

Cov.:

AF XY:

0.0147

AC XY:

10669

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.00454

Gnomad4 AMR exome

AF:

0.0108

Gnomad4 ASJ exome

AF:

0.0275

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00333

Gnomad4 FIN exome

AF:

0.0169

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0124

AC:

1895

AN:

152276

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

926

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0213

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0185

EpiControl

AF:

0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Early infantile epileptic encephalopathy with suppression bursts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.8

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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