chr11-100722807-G-C

Variant names:

• chr11-100722807-G-C
• rs633185
• NM_152432.4:c.154+34975G>C

Variant summary

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

The NM_152432.4(ARHGAP42):​c.154+34975G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,108 control chromosomes in the GnomAD database, including 39,173 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 0.71 (39173 hom., cov: 33)
• Consequence: ARHGAP42 NM_152432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781
• Publications: 88 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 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.154+34975G>C		intron	N/A	NP_689645.2
	ARHGAP42	NM_001367945.1		c.-429+34975G>C		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.154+34975G>C		intron	N/A	ENSP00000298815.7
	ARHGAP42	ENST00000524892.7	TSL:5	c.154+34975G>C		intron	N/A	ENSP00000431776.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108431 AN: 151988 Hom.: 39148 Cov.: 33

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.713 AC: 108518 AN: 152108 Hom.: 39173 Cov.: 33 AF XY: 0.707 AC XY: 52582 AN XY: 74370

African (AFR) AF: 0.796 AC: 33067 AN: 41516

American (AMR) AF: 0.618 AC: 9445 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2481 AN: 3468

East Asian (EAS) AF: 0.498 AC: 2570 AN: 5158

South Asian (SAS) AF: 0.548 AC: 2636 AN: 4814

European-Finnish (FIN) AF: 0.704 AC: 7432 AN: 10564

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48584 AN: 67990

Other (OTH) AF: 0.720 AC: 1524 AN: 2116

Alfa AF: 0.689 Hom.: 17691

Bravo AF: 0.709

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.58
PhyloP100		-0.78
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: rs633185; hg19: chr11-100593538;