12-57613895-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182947.4(ARHGEF25):​c.553-121G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000609 in 1,313,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000061 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF25	NM_182947.4	c.553-121G>T		intron_variant	Intron 5 of 14	ENST00000286494.9	NP_891992.3
ARHGEF25	NM_001111270.3	c.670-121G>T		intron_variant	Intron 6 of 15		NP_001104740.2
ARHGEF25	NM_001347933.2	c.553-121G>T		intron_variant	Intron 5 of 13		NP_001334862.2
ARHGEF25	NR_046223.2	n.1043-121G>T		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>T		intron_variant	Intron 5 of 14	1	NM_182947.4	ENSP00000286494.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000609 AC: 8 AN: 1313558 Hom.: 0 Cov.: 20 AF XY: 0.00000763 AC XY: 5 AN XY: 655488

African (AFR) AF: 0.00 AC: 0 AN: 30630

American (AMR) AF: 0.00 AC: 0 AN: 41284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22900

East Asian (EAS) AF: 0.00 AC: 0 AN: 38884

South Asian (SAS) AF: 0.00 AC: 0 AN: 77852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4526

European-Non Finnish (NFE) AF: 0.00000606 AC: 6 AN: 990834

Other (OTH) AF: 0.0000363 AC: 2 AN: 55040

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.89
PhyloP100		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;