11-100706252-C-T

Position:

• chr11-100706252-C-T

Variant summary

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

The NM_152432.4(ARHGAP42):​c.154+18420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 152,298 control chromosomes in the GnomAD database, including 47 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 0.0057 (47 hom., cov: 33)
• Consequence: ARHGAP42 NM_152432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP42	NM_152432.4	c.154+18420C>T		intron_variant		ENST00000298815.13	NP_689645.2
ARHGAP42	NM_001367945.1	c.-429+18420C>T		intron_variant			NP_001354874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP42	ENST00000298815.13	c.154+18420C>T		intron_variant		5	NM_152432.4	ENSP00000298815	P1
ARHGAP42	ENST00000524892.7	c.154+18420C>T		intron_variant		5		ENSP00000431776

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 880 AN: 152180 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00382

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

GnomAD4 genome AF: 0.00571 AC: 869 AN: 152298 Hom.: 47 Cov.: 33 AF XY: 0.00642 AC XY: 478 AN XY: 74466

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000510 Hom.: 0

Bravo AF: 0.00653

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.49

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: rs11224401; hg19: chr11-100576983;