NM_182947.4:c.553-121G>A

Variant names:

• chr12-57613895-G-A
• rs7305391
• NM_182947.4:c.553-121G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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:41260):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARHGEF25	NM_182947.4	c.553-121G>A		intron_variant	Intron 5 of 14	ENST00000286494.9	NP_891992.3
ARHGEF25	NM_001111270.3	c.670-121G>A		intron_variant	Intron 6 of 15		NP_001104740.2
ARHGEF25	NM_001347933.2	c.553-121G>A		intron_variant	Intron 5 of 13		NP_001334862.2
ARHGEF25	NR_046223.2	n.1043-121G>A		intron_variant	Intron 6 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF25	ENST00000286494.9	c.553-121G>A		intron_variant	Intron 5 of 14	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

African (AFR) AF: 0.0358 AC: 1097 AN: 30614

American (AMR) AF: 0.136 AC: 5591 AN: 41256

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 4486 AN: 22886

East Asian (EAS) AF: 0.185 AC: 7188 AN: 38874

South Asian (SAS) AF: 0.148 AC: 11514 AN: 77816

European-Finnish (FIN) AF: 0.261 AC: 13464 AN: 51592

Middle Eastern (MID) AF: 0.181 AC: 819 AN: 4522

European-Non Finnish (NFE) AF: 0.234 AC: 231627 AN: 989380

Other (OTH) AF: 0.203 AC: 11149 AN: 54960

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

African (AFR) AF: 0.0413 AC: 1711 AN: 41462

American (AMR) AF: 0.152 AC: 2323 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3466

East Asian (EAS) AF: 0.175 AC: 897 AN: 5138

South Asian (SAS) AF: 0.159 AC: 763 AN: 4798

European-Finnish (FIN) AF: 0.259 AC: 2735 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15767 AN: 67916

Other (OTH) AF: 0.194 AC: 409 AN: 2104

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
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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