12-57613895-G-A

Position:

• chr12-57613895-G-A

Variant summary

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

The NM_182947.4(ARHGEF25):​c.553-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,463,824 control chromosomes in the GnomAD database, including 35,749 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 (2652 hom., cov: 31)
  • Exomes 𝑓: 0.22 (33097 hom.)
• Consequence: ARHGEF25 NM_182947.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

ARHGEF25 (HGNC:30275): (Rho guanine nucleotide exchange factor 25) Rho GTPases alternate between an inactive GDP-bound state and an active GTP-bound state, and GEFs facilitate GDP/GTP exchange. This gene encodes a guanine nucleotide exchange factor (GEF) which interacts with Rho GTPases involved in contraction of vascular smooth muscles, regulation of responses to angiotensin II and lens cell differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ENSG00000224713 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF25	NM_182947.4	c.553-121G>A		intron_variant		ENST00000286494.9	NP_891992.3
ARHGEF25	NM_001111270.3	c.670-121G>A		intron_variant			NP_001104740.2
ARHGEF25	NM_001347933.2	c.553-121G>A		intron_variant			NP_001334862.2
ARHGEF25	NR_046223.2	n.1043-121G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF25	ENST00000286494.9	c.553-121G>A		intron_variant		1	NM_182947.4	ENSP00000286494.4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25463 AN: 151806 Hom.: 2651 Cov.: 31

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.219 AC: 286935 AN: 1311900 Hom.: 33097 Cov.: 20 AF XY: 0.217 AC XY: 141966 AN XY: 654696

Gnomad4 AFR exome AF: 0.0358

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.168 AC: 25471 AN: 151924 Hom.: 2652 Cov.: 31 AF XY: 0.169 AC XY: 12513 AN XY: 74248

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.194

Alfa AF: 0.152 Hom.: 454

Bravo AF: 0.155

Asia WGS AF: 0.160 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.85

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: rs7305391; hg19: chr12-58007678; COSMIC: COSV54087232; COSMIC: COSV54087232;