8-1857879-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.598

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.38-81G>T		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.38-81G>T		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.110-81G>T		intron_variant		1
ARHGEF10	ENST00000520359.5	c.38-81G>T		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.110-81G>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 51372 AN: 113250 Hom.: 9057 Cov.: 18

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

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.: 18 AF XY: 0.456 AC XY: 25080 AN XY: 54956

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

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

Other links and lift over

dbSNP: rs11268265; hg19: chr8-1806045; COSMIC: COSV50642272; COSMIC: COSV50642272;