chr4-147869497-A-G

Variant names:

• chr4-147869497-A-G
• rs2118034
• NM_024605.4:c.702+2681A>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.702+2681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,210 control chromosomes in the GnomAD database, including 68,587 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 0.95 (68587 hom., cov: 31)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP10	NM_024605.4	c.702+2681A>G		intron_variant	Intron 7 of 22	ENST00000336498.8	NP_078881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.702+2681A>G		intron_variant	Intron 7 of 22	1	NM_024605.4	ENSP00000336923.3
ARHGAP10	ENST00000506054.5	n.5834+2681A>G		intron_variant	Intron 1 of 16	1

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143919 AN: 152092 Hom.: 68533 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.952

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.955

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

GnomAD4 genome AF: 0.946 AC: 144029 AN: 152210 Hom.: 68587 Cov.: 31 AF XY: 0.948 AC XY: 70544 AN XY: 74450

African (AFR) AF: 0.825 AC: 34228 AN: 41476

American (AMR) AF: 0.977 AC: 14947 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3445 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5106 AN: 5182

South Asian (SAS) AF: 0.952 AC: 4591 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10605 AN: 10608

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67900 AN: 68034

Other (OTH) AF: 0.954 AC: 2015 AN: 2112

Alfa AF: 0.978 Hom.: 230660

Bravo AF: 0.939

Asia WGS AF: 0.951 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.4
DANN	Benign	0.80
PhyloP100		0.17
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: rs2118034; hg19: chr4-148790648;