rs9560010

Positions:

• chr13-111214173-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354046.2(ARHGEF7):​c.469-3506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,130 control chromosomes in the GnomAD database, including 3,031 homozygotes. 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: 𝑓 0.17 (3031 hom., cov: 32)
• Consequence: ARHGEF7 NM_001354046.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

Genes affected

ARHGEF7 (HGNC:15607): (Rho guanine nucleotide exchange factor 7) This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF7	NM_001354046.2	c.469-3506G>A		intron_variant		ENST00000646102.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF7	ENST00000646102.2	c.469-3506G>A		intron_variant			NM_001354046.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25306 AN: 152012 Hom.: 3021 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25344 AN: 152130 Hom.: 3031 Cov.: 32 AF XY: 0.174 AC XY: 12934 AN XY: 74362

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.164

Alfa AF: 0.156 Hom.: 1917

Bravo AF: 0.164

Asia WGS AF: 0.439 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.72

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: rs9560010; hg19: chr13-111866520;