rs10519931

Variant names:

• chr4-148062225-A-G
• rs10519931
• NM_024605.4:c.2028-923A>G

Variant summary

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

The NM_024605.4(ARHGAP10):​c.2028-923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,210 control chromosomes in the GnomAD database, including 1,104 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 0.11 (1104 hom., cov: 32)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP10	NM_024605.4	c.2028-923A>G		intron_variant	Intron 20 of 22	ENST00000336498.8	NP_078881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.2028-923A>G		intron_variant	Intron 20 of 22	1	NM_024605.4	ENSP00000336923.3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17254 AN: 152092 Hom.: 1104 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0781

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.113 AC: 17264 AN: 152210 Hom.: 1104 Cov.: 32 AF XY: 0.111 AC XY: 8295 AN XY: 74430

African (AFR) AF: 0.0807 AC: 3354 AN: 41536

American (AMR) AF: 0.102 AC: 1562 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0790 AC: 381 AN: 4822

European-Finnish (FIN) AF: 0.105 AC: 1113 AN: 10600

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9754 AN: 67992

Other (OTH) AF: 0.138 AC: 290 AN: 2106

Alfa AF: 0.141 Hom.: 2678

Bravo AF: 0.112

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.56
PhyloP100		-1.0
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: rs10519931; hg19: chr4-148983376;