rs2164531

Positions:

• chr4-147929816-A-G

Variant summary

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

The NM_024605.4(ARHGAP10):​c.1229-10009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,210 control chromosomes in the GnomAD database, including 2,276 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 0.12 (2276 hom., cov: 33)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP10	NM_024605.4	c.1229-10009A>G		intron_variant		ENST00000336498.8	NP_078881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.1229-10009A>G		intron_variant		1	NM_024605.4	ENSP00000336923	P1
ARHGAP10	ENST00000506054.5	n.6361-10009A>G		intron_variant, non_coding_transcript_variant		1
ARHGAP10	ENST00000507661.1	c.261-10009A>G		intron_variant		2		ENSP00000422358

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17662 AN: 152092 Hom.: 2270 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0987

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

GnomAD4 genome AF: 0.116 AC: 17701 AN: 152210 Hom.: 2276 Cov.: 33 AF XY: 0.116 AC XY: 8630 AN XY: 74432

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0655 Hom.: 142

Bravo AF: 0.140

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.74

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: rs2164531; hg19: chr4-148850967;