chr11-73325436-G-A

Position:

• chr11-73325436-G-A

Variant summary

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

The NM_014786.4(ARHGEF17):​c.3192+13606G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,120 control chromosomes in the GnomAD database, including 2,958 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 0.17 (2958 hom., cov: 32)
• Consequence: ARHGEF17 NM_014786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

Genes affected

ARHGEF17 (HGNC:21726): (Rho guanine nucleotide exchange factor 17) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within actin cytoskeleton organization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF17	NM_014786.4	c.3192+13606G>A		intron_variant		ENST00000263674.4	NP_055601.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF17	ENST00000263674.4	c.3192+13606G>A		intron_variant		1	NM_014786.4	ENSP00000263674	P1
ARHGEF17	ENST00000544519.1	c.266+13606G>A		intron_variant		4		ENSP00000441135

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25661 AN: 152002 Hom.: 2936 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.169 AC: 25720 AN: 152120 Hom.: 2958 Cov.: 32 AF XY: 0.168 AC XY: 12530 AN XY: 74376

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0416

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.138

Alfa AF: 0.147 Hom.: 267

Bravo AF: 0.169

Asia WGS AF: 0.0980 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.65

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: rs2027760; hg19: chr11-73036481;