chr11-73308819-C-G

Variant names:

• chr11-73308819-C-G
• rs993055517
• NM_014786.4:c.181C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014786.4(ARHGEF17):​c.181C>G​(p.Leu61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF17 NM_014786.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.517
• Publications: 0 publications found

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]

ARHGEF17-AS1 (HGNC:55485): (ARHGEF17 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19937056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF17	NM_014786.4	MANE Select	c.181C>G	p.Leu61Val	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.543G>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF17	ENST00000263674.4	TSL:1 MANE Select	c.181C>G	p.Leu61Val	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
	ARHGEF17	ENST00000914587.1		c.181C>G	p.Leu61Val	missense	Exon 1 of 20	ENSP00000584647.1
	ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.543G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2872 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1197636 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 579022

African (AFR) AF: 0.00 AC: 0 AN: 23524

American (AMR) AF: 0.00 AC: 0 AN: 9202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16716

East Asian (EAS) AF: 0.00 AC: 0 AN: 27022

South Asian (SAS) AF: 0.00 AC: 0 AN: 49824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3416

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 989786

Other (OTH) AF: 0.00 AC: 0 AN: 49206

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152102 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.021
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.52
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.059
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.23	T
Polyphen		0.63	P
Vest4		0.18
MutPred		0.28		Gain of methylation at K60 (P = 0.0336)
MVP		0.33
MPC		1.1
ClinPred		0.56	D
GERP RS		2.6
Varity_R		0.21
gMVP		0.20
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs993055517; hg19: chr11-73019864;