Genetic Variant NM_014629.4:c.37+36T>G (chr8-1843472-T-G) – 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.37+36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,536,610 control chromosomes in the GnomAD database, including 227,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17131 hom., cov: 32)

Exomes 𝑓: 0.55 ( 210152 hom. )

Consequence

ARHGEF10
NM_014629.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.428

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 8-1843472-T-G is Benign according to our data. Variant chr8-1843472-T-G is described in ClinVar as [Benign]. Clinvar id is 1292938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.37+36T>G		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.37+36T>G		intron_variant	Intron 2 of 28	1	NM_014629.4	ENSP00000340297.3		O15013-5
KBTBD11-OT1	ENST00000635855.1 link	n.627+36T>G		intron_variant	Intron 3 of 29	5		ENSP00000489726.1		A0A1B0GTJ5

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68541

AN:

151850

Hom.:

17131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.400

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.482

AC:

116069

AN:

240852

Hom.:

29248

AF XY:

0.488

AC XY:

63714

AN XY:

130436

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.389

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.570

Gnomad NFE exome

AF:

0.558

Gnomad OTH exome

AF:

0.487

GnomAD4 exome

AF:

0.545

AC:

754845

AN:

1384640

Hom.:

210152

Cov.:

AF XY:

0.542

AC XY:

375524

AN XY:

692858

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.382

Gnomad4 ASJ exome

AF:

0.465

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.576

Gnomad4 OTH exome

AF:

0.515

GnomAD4 genome

AF:

0.451

AC:

68563

AN:

151970

Hom.:

17131

Cov.:

AF XY:

0.450

AC XY:

33412

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.456

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.547

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.506

Hom.:

3785

Bravo

AF:

0.427

Asia WGS

AF:

0.467

AC:

1624

AN:

3478

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

-1.0

CADD

Benign

5.2

DANN

Benign

0.52

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