2-68786119-C-T

Variant names:

• chr2-68786119-C-T
• rs11694785
• NM_001007231.3:c.350-1721C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007231.3(ARHGAP25):​c.350-1721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,990 control chromosomes in the GnomAD database, including 12,856 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 0.41 (12856 hom., cov: 32)
• Consequence: ARHGAP25 NM_001007231.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 4 publications found

Genes affected

ARHGAP25 (HGNC:28951): (Rho GTPase activating protein 25) ARHGAPs, such as ARHGAP25, encode negative regulators of Rho GTPases (see ARHA; MIM 165390), which are implicated in actin remodeling, cell polarity, and cell migration (Katoh and Katoh, 2004 [PubMed 15254788]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007231.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP25	NM_001007231.3	MANE Select	c.350-1721C>T		intron	N/A	NP_001007232.2
	ARHGAP25	NM_001364819.1		c.350-1721C>T		intron	N/A	NP_001351748.1
	ARHGAP25	NM_001166276.2		c.329-1721C>T		intron	N/A	NP_001159748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP25	ENST00000409202.8	TSL:2 MANE Select	c.350-1721C>T		intron	N/A	ENSP00000386911.3
	ARHGAP25	ENST00000409220.5	TSL:1	c.329-1721C>T		intron	N/A	ENSP00000386241.1
	ARHGAP25	ENST00000409030.7	TSL:1	c.329-1721C>T		intron	N/A	ENSP00000386863.3

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62003 AN: 151872 Hom.: 12851 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.408 AC: 62039 AN: 151990 Hom.: 12856 Cov.: 32 AF XY: 0.408 AC XY: 30326 AN XY: 74302

African (AFR) AF: 0.394 AC: 16340 AN: 41460

American (AMR) AF: 0.382 AC: 5836 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3466

East Asian (EAS) AF: 0.309 AC: 1598 AN: 5164

South Asian (SAS) AF: 0.380 AC: 1827 AN: 4814

European-Finnish (FIN) AF: 0.461 AC: 4860 AN: 10544

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28602 AN: 67940

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.324 Hom.: 1265

Bravo AF: 0.400

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.38
PhyloP100		-1.4
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: rs11694785; hg19: chr2-69013251;