rs10488786

Positions:

• chr11-100869463-G-A
• chr11-100869463-G-T

Variant summary

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

The NM_152432.4(ARHGAP42):​c.384+9838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 147,064 control chromosomes in the GnomAD database, including 514 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 0.072 (514 hom., cov: 31)
• Consequence: ARHGAP42 NM_152432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801

Genes affected

ARHGAP42 (HGNC:26545): (Rho GTPase activating protein 42) This gene encodes a Rho GTPase-activating protein (RhoGAP), and member of the GRAF or BAR-PH family of proteins. Expression of this gene is enriched in vascular smooth muscle cells and the encoded protein inhibits RhoA activity to regulate vascular tone and control blood pressure. A mutation in the first intron of this gene modulates its expression and is associated with reduced blood pressure in human patients with borderline hypertension. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP42	NM_152432.4	c.384+9838G>A		intron_variant		ENST00000298815.13	NP_689645.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP42	ENST00000298815.13	c.384+9838G>A		intron_variant		5	NM_152432.4	ENSP00000298815	P1
ARHGAP42	ENST00000524892.7	c.384+9838G>A		intron_variant		5		ENSP00000431776
ARHGAP42	ENST00000529406.5	n.374+9838G>A		intron_variant, non_coding_transcript_variant		3
ARHGAP42	ENST00000534060.5	n.428+9838G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10627 AN: 146956 Hom.: 517 Cov.: 31

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0828

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.0865

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

GnomAD4 genome AF: 0.0722 AC: 10621 AN: 147064 Hom.: 514 Cov.: 31 AF XY: 0.0738 AC XY: 5271 AN XY: 71380

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.0933

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.0828

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.0781 Hom.: 283

Bravo AF: 0.0699

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.65

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: rs10488786; hg19: chr11-100740194;