rs2635266

Positions:

• chr4-147945375-G-A
• chr4-147945375-G-C
• chr4-147945375-G-T

Variant summary

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

The NM_024605.4(ARHGAP10):​c.1304-1242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,046 control chromosomes in the GnomAD database, including 46,994 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 0.75 (46994 hom., cov: 31)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

Genes affected

ARHGAP10 (HGNC:26099): (Rho GTPase activating protein 10) Predicted to enable GTPase activator activity. Predicted to be involved in cytoskeleton organization and negative regulation of apoptotic process. Predicted to be located in perinuclear region of cytoplasm and plasma membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP10	NM_024605.4	c.1304-1242G>A		intron_variant		ENST00000336498.8	NP_078881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.1304-1242G>A		intron_variant		1	NM_024605.4	ENSP00000336923	P1
ARHGAP10	ENST00000506054.5	n.6436-1242G>A		intron_variant, non_coding_transcript_variant		1
ARHGAP10	ENST00000507661.1	c.336-1242G>A		intron_variant		2		ENSP00000422358

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114289 AN: 151928 Hom.: 46999 Cov.: 31

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.926

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.752 AC: 114308 AN: 152046 Hom.: 46994 Cov.: 31 AF XY: 0.756 AC XY: 56162 AN XY: 74330

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.926

Gnomad4 OTH AF: 0.791

Alfa AF: 0.884 Hom.: 62796

Bravo AF: 0.722

Asia WGS AF: 0.720 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.58
DANN	Benign	0.51

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: rs2635266; hg19: chr4-148866526;