Genetic Variant NM_014629.4:c.38-81G>T (chr8-1857879-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014629.4(ARHGEF10):c.38-81G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 9063 hom., cov: 18)

Exomes 𝑓: 0.40 ( 27119 hom. )

Failed GnomAD Quality Control

Consequence

ARHGEF10
NM_014629.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.598

Variant links:

Genes affected

ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ARHGEF10 links:

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

BP6

Variant 8-1857879-G-T is Benign according to our data. Variant chr8-1857879-G-T is described in ClinVar as [Benign]. Clinvar id is 1292935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.38-81G>T		intron_variant	Intron 2 of 28	ENST00000349830.8	NP_055444.2	O15013-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8 link	c.38-81G>T		intron_variant	Intron 2 of 28	1	NM_014629.4	ENSP00000340297.3		O15013-5
KBTBD11-OT1	ENST00000635855.1 link	n.628-81G>T		intron_variant	Intron 3 of 29	5		ENSP00000489726.1		A0A1B0GTJ5

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

51372

AN:

113250

Hom.:

9057

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.374

Gnomad NFE

AF:

0.462

Gnomad OTH

AF:

0.414

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.397

AC:

189739

AN:

477786

Hom.:

27119

AF XY:

0.399

AC XY:

101237

AN XY:

253612

show subpopulations

Gnomad4 AFR exome

AF:

0.361

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.454

AC:

51401

AN:

113320

Hom.:

9063

Cov.:

AF XY:

0.456

AC XY:

25080

AN XY:

54956

show subpopulations

Gnomad4 AFR

AF:

0.417

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.353

Gnomad4 EAS

AF:

0.452

Gnomad4 SAS

AF:

0.517

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.462

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.581

Hom.:

3418

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.044

DANN

Benign

0.37

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