rs594624

Positions:

• chr11-110598602-A-G

Variant summary

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

The NM_001384657.1(ARHGAP20):​c.965-6447T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,080 control chromosomes in the GnomAD database, including 10,639 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 0.33 (10639 hom., cov: 32)
• Consequence: ARHGAP20 NM_001384657.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP20	NM_001384657.1	c.965-6447T>C		intron_variant		ENST00000683387.1	NP_001371586.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP20	ENST00000683387.1	c.965-6447T>C		intron_variant			NM_001384657.1	ENSP00000507405.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50186 AN: 151964 Hom.: 10601 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.331 AC: 50280 AN: 152080 Hom.: 10639 Cov.: 32 AF XY: 0.328 AC XY: 24409 AN XY: 74340

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.283

Alfa AF: 0.260 Hom.: 3487

Bravo AF: 0.333

Asia WGS AF: 0.282 AC: 981 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	3.2
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: rs594624; hg19: chr11-110469326;