Variant 1-17607948-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018125.4(ARHGEF10L):c.580G>A(p.Ala194Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,440,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

ARHGEF10L
NM_018125.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0570

Variant links:

Genes affected

ARHGEF10L (HGNC:25540): (Rho guanine nucleotide exchange factor 10 like) This gene belongs to the RhoGEF subfamily of RhoGTPases. Members of this subfamily are activated by specific guanine nucleotide exchange factors (GEFs) and are involved in signal transduction. The encoded protein shows cytosolic distribution. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2016]

ARHGEF10L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027739018).

BP6

Variant 1-17607948-G-A is Benign according to our data. Variant chr1-17607948-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2591237.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10L	NM_018125.4 linkuse as main transcript	c.580G>A	p.Ala194Thr	missense_variant	7/29	ENST00000361221.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10L	ENST00000361221.8 linkuse as main transcript	c.580G>A	p.Ala194Thr	missense_variant	7/29	1	NM_018125.4	A1	Q9HCE6-1
ARHGEF10L	ENST00000375415.5 linkuse as main transcript	c.580G>A	p.Ala194Thr	missense_variant	6/27	1		P4	Q9HCE6-2

Frequencies

GnomAD3 genomes

AF:

0.0000669

AC:

AN:

149532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000697

AC:

AN:

1291088

Hom.:

Cov.:

AF XY:

0.00000474

AC XY:

AN XY:

633120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000406

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000588

Gnomad4 OTH exome

AF:

0.0000193

GnomAD4 genome

AF:

0.0000669

AC:

AN:

149532

Hom.:

Cov.:

AF XY:

0.0000822

AC XY:

AN XY:

72984

show subpopulations

Gnomad4 AFR

AF:

0.000171

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.097

DANN

Benign

0.70

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

N;N

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.57

N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.0050

B;B

Vest4

0.099

MVP

0.040

MPC

0.052

ClinPred

0.025

GERP RS

-6.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over