rs326946

Positions:

• chr11-110628530-A-C

Variant summary

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

The NM_001384657.1(ARHGAP20):​c.353+2098T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,582 control chromosomes in the GnomAD database, including 7,226 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 0.26 (7226 hom., cov: 31)
• Consequence: ARHGAP20 NM_001384657.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

Genes affected

ARHGAP20 (HGNC:18357): (Rho GTPase activating protein 20) The protein encoded by this gene is an activator of RHO-type GTPases, transducing a signal from RAP1 to RHO and impacting neurite outgrowth. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP20	NM_001384657.1	c.353+2098T>G		intron_variant		ENST00000683387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP20	ENST00000683387.1	c.353+2098T>G		intron_variant			NM_001384657.1	P4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38752 AN: 151466 Hom.: 7202 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.256 AC: 38824 AN: 151582 Hom.: 7226 Cov.: 31 AF XY: 0.255 AC XY: 18923 AN XY: 74072

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.225

Alfa AF: 0.159 Hom.: 2918

Bravo AF: 0.262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.75
DANN	Benign	0.50

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: rs326946; hg19: chr11-110499253; COSMIC: COSV52810094;