rs766441392

Variant names:

• chr17-8312100-C-A
• NM_173728.4:c.61C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-8312100-C-A
• chr17-8312100-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173728.4(ARHGEF15):​c.61C>A​(p.Arg21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,346,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ARHGEF15 NM_173728.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3945613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF15	NM_173728.4	c.61C>A	p.Arg21Ser	missense_variant	Exon 2 of 16	ENST00000361926.8	NP_776089.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF15	ENST00000361926.8	c.61C>A	p.Arg21Ser	missense_variant	Exon 2 of 16	1	NM_173728.4	ENSP00000355026.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1346548 Hom.: 0 Cov.: 35 AF XY: 0.00000149 AC XY: 1 AN XY: 670478

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000282

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Benign	0.93
DEOGEN2	Benign	0.055	.;T;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.79	T;.;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.0	.;M;.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.57	.;N;.;N
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	.;D;.;D
Sift4G	Benign	0.92	T;T;T;T
Polyphen		1.0	.;D;.;D
Vest4		0.44, 0.45
MutPred		0.34		Gain of phosphorylation at R21 (P = 4e-04);Gain of phosphorylation at R21 (P = 4e-04);Gain of phosphorylation at R21 (P = 4e-04);Gain of phosphorylation at R21 (P = 4e-04);
MVP		0.86
MPC		0.46
ClinPred		0.88	D
GERP RS		5.0
Varity_R		0.38
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8215418;