11-100869463-G-A

Variant names:

• chr11-100869463-G-A
• rs10488786
• NM_152432.4:c.384+9838G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000308705 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152432.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP42	NM_152432.4	MANE Select	c.384+9838G>A		intron	N/A	NP_689645.2
	ARHGAP42	NM_001367945.1		c.102+9838G>A		intron	N/A	NP_001354874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP42	ENST00000298815.13	TSL:5 MANE Select	c.384+9838G>A		intron	N/A	ENSP00000298815.7
	ENSG00000308705	ENST00000835902.1		n.1031G>A		non_coding_transcript_exon	Exon 2 of 2
	ARHGAP42	ENST00000524892.7	TSL:5	c.384+9838G>A		intron	N/A	ENSP00000431776.1

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

African (AFR) AF: 0.0180 AC: 715 AN: 39678

American (AMR) AF: 0.0867 AC: 1280 AN: 14770

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 352 AN: 3436

East Asian (EAS) AF: 0.250 AC: 1259 AN: 5032

South Asian (SAS) AF: 0.0933 AC: 436 AN: 4674

European-Finnish (FIN) AF: 0.0809 AC: 754 AN: 9318

Middle Eastern (MID) AF: 0.122 AC: 35 AN: 286

European-Non Finnish (NFE) AF: 0.0828 AC: 5539 AN: 66920

Other (OTH) AF: 0.0861 AC: 176 AN: 2044

Alfa AF: 0.0776 Hom.: 310

Bravo AF: 0.0699

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.65
PhyloP100		-0.80
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: rs10488786; hg19: chr11-100740194;