rs11224447

Positions:

• chr11-100789108-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.251-5997G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,166 control chromosomes in the GnomAD database, including 343 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 0.067 (343 hom., cov: 33)
• Consequence: ARHGAP42 NM_152432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP42	NM_152432.4	c.251-5997G>T		intron_variant		ENST00000298815.13
ARHGAP42	NM_001367945.1	c.-332-5997G>T		intron_variant
ARHGAP42	XM_011542615.3	c.89-5997G>T		intron_variant
ARHGAP42	XM_011542616.3	c.89-5997G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP42	ENST00000298815.13	c.251-5997G>T		intron_variant		5	NM_152432.4	P1

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10237 AN: 152048 Hom.: 346 Cov.: 33

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0656

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

GnomAD4 genome AF: 0.0673 AC: 10239 AN: 152166 Hom.: 343 Cov.: 33 AF XY: 0.0674 AC XY: 5015 AN XY: 74388

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.0550

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0916

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0602

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0620 Hom.: 47

Bravo AF: 0.0663

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.80
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11224447; hg19: chr11-100659839;