11-100772692-A-T

Variant names:

• chr11-100772692-A-T
• rs4121392
• NM_152432.4:c.250+2254A>T

Variant summary

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

The NM_152432.4(ARHGAP42):​c.250+2254A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,130 control chromosomes in the GnomAD database, including 6,718 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 0.29 (6718 hom., cov: 33)
• Consequence: ARHGAP42 NM_152432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP42	NM_152432.4	c.250+2254A>T		intron_variant	Intron 2 of 23	ENST00000298815.13	NP_689645.2
ARHGAP42	NM_001367945.1	c.-333+2254A>T		intron_variant	Intron 2 of 25		NP_001354874.1
ARHGAP42	XM_011542615.3	c.88+2254A>T		intron_variant	Intron 2 of 23		XP_011540917.1
ARHGAP42	XM_011542616.3	c.88+2254A>T		intron_variant	Intron 2 of 23		XP_011540918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP42	ENST00000298815.13	c.250+2254A>T		intron_variant	Intron 2 of 23	5	NM_152432.4	ENSP00000298815.7

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44024 AN: 152012 Hom.: 6717 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.290 AC: 44048 AN: 152130 Hom.: 6718 Cov.: 33 AF XY: 0.284 AC XY: 21141 AN XY: 74362

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.274

Alfa AF: 0.175 Hom.: 334

Bravo AF: 0.289

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.73
DANN	Benign	0.47

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: rs4121392; hg19: chr11-100643423;