rs7658486

Positions:

• chr4-147963038-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	UniProt
ARHGAP10	NM_024605.4	c.1451-1986C>T		intron_variant		ENST00000336498.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP10	ENST00000336498.8	c.1451-1986C>T		intron_variant		1	NM_024605.4	P1
ARHGAP10	ENST00000506020.5	n.526-1986C>T		intron_variant, non_coding_transcript_variant		1
ARHGAP10	ENST00000506054.5	n.6583-1986C>T		intron_variant, non_coding_transcript_variant		1
ARHGAP10	ENST00000507661.1	c.483-1986C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0478

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0457 Hom.: 393

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

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: rs7658486; hg19: chr4-148884189;