rs717225

Positions:

• chr19-41889215-A-G

Variant summary

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

The NM_004706.4(ARHGEF1):​c.225+350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 213,628 control chromosomes in the GnomAD database, including 11,544 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 0.22 (10727 hom., cov: 32)
  • Exomes 𝑓: 0.063 (817 hom.)
• Consequence: ARHGEF1 NM_004706.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940

Genes affected

ARHGEF1 (HGNC:681): (Rho guanine nucleotide exchange factor 1) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

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 (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF1	NM_004706.4	c.225+350A>G		intron_variant		ENST00000354532.8	NP_004697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF1	ENST00000354532.8	c.225+350A>G		intron_variant		1	NM_004706.4	ENSP00000346532	A1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33732 AN: 152010 Hom.: 10688 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.00637

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.0632 AC: 3885 AN: 61500 Hom.: 817 Cov.: 0 AF XY: 0.0603 AC XY: 1929 AN XY: 32012

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.0568

Gnomad4 ASJ exome AF: 0.0470

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.0971

Gnomad4 FIN exome AF: 0.0427

Gnomad4 NFE exome AF: 0.00473

Gnomad4 OTH exome AF: 0.0777

GnomAD4 genome AF: 0.222 AC: 33832 AN: 152128 Hom.: 10727 Cov.: 32 AF XY: 0.221 AC XY: 16433 AN XY: 74404

Gnomad4 AFR AF: 0.703

Gnomad4 AMR AF: 0.0862

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0542

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.174

Alfa AF: 0.0453 Hom.: 3323

Bravo AF: 0.246

Asia WGS AF: 0.264 AC: 918 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	1.0
DANN	Benign	0.69

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: rs717225; hg19: chr19-42393286; COSMIC: COSV61529620; COSMIC: COSV61529620;