rs9890841

Variant names:

• chr17-8312256-C-G
• rs9890841
• NM_173728.4:c.217C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-8312256-C-G
• chr17-8312256-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173728.4(ARHGEF15):​c.217C>G​(p.Pro73Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000764 in 1,309,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P73S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ARHGEF15 NM_173728.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21666953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF15	NM_173728.4	c.217C>G	p.Pro73Ala	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.217C>G	p.Pro73Ala	missense_variant	Exon 2 of 16	1	NM_173728.4	ENSP00000355026.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.64e-7 AC: 1 AN: 1309364 Hom.: 0 Cov.: 36 AF XY: 0.00000155 AC XY: 1 AN XY: 646818

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 29594

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 36962

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 18532

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35320

Gnomad4 SAS exome AF: 0.0000131 AC: 1 AN: 76478

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 41944

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1014262

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 51338

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Benign	0.80
DEOGEN2	Benign	0.055	.;T;.;T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T;.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.0	.;L;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	.;N;.;N
REVEL	Benign	0.066
Sift	Uncertain	0.0020	.;D;.;D
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.32	.;B;.;B
Vest4		0.28
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);
MVP		0.76
MPC		0.44
ClinPred		0.70	D
GERP RS		4.7
Varity_R		0.11
gMVP		0.14

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

Other links and lift over

dbSNP: rs9890841; hg19: chr17-8215574;