rs7658486

Variant names:

• chr4-147963038-C-T
• rs7658486
• NM_024605.4:c.1451-1986C>T

Variant summary

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

The NM_024605.4(ARHGAP10):​c.1451-1986C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0736 in 152,168 control chromosomes in the GnomAD database, including 692 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 0.074 (692 hom., cov: 32)
• Consequence: ARHGAP10 NM_024605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP10	NM_024605.4	c.1451-1986C>T		intron_variant	Intron 16 of 22	ENST00000336498.8	NP_078881.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.1451-1986C>T		intron_variant	Intron 16 of 22	1	NM_024605.4	ENSP00000336923.3
ARHGAP10	ENST00000506020.5	n.526-1986C>T		intron_variant	Intron 2 of 8	1
ARHGAP10	ENST00000506054.5	n.6583-1986C>T		intron_variant	Intron 10 of 16	1
ARHGAP10	ENST00000507661.1	c.482-1986C>T		intron_variant	Intron 7 of 12	2		ENSP00000422358.1

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11163 AN: 152050 Hom.: 684 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0736 AC: 11204 AN: 152168 Hom.: 692 Cov.: 32 AF XY: 0.0717 AC XY: 5332 AN XY: 74400

African (AFR) AF: 0.168 AC: 6956 AN: 41490

American (AMR) AF: 0.0513 AC: 784 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.0478 AC: 248 AN: 5186

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4822

European-Finnish (FIN) AF: 0.0164 AC: 174 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2476 AN: 68008

Other (OTH) AF: 0.0672 AC: 142 AN: 2112

Alfa AF: 0.0495 Hom.: 1113

Bravo AF: 0.0821

Asia WGS AF: 0.0770 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.81
PhyloP100		0.25
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: rs7658486; hg19: chr4-148884189;