8-1857875-GATCGATCT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014629.4(ARHGEF10):c.38-81_38-74del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 898,300 control chromosomes in the GnomAD database, including 1,210 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (445 hom., cov: 18)
  • Exomes 𝑓: 0.047 (765 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10

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 -10 ACMG points.

• BP6: Variant 8-1857875-GATCGATCT-G is Benign according to our data. Variant chr8-1857875-GATCGATCT-G is described in ClinVar as [Benign]. Clinvar id is 1249869.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.38-81_38-74del		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.38-81_38-74del		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.110-81_110-74del		intron_variant		1
ARHGEF10	ENST00000520359.5	c.38-81_38-74del		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.110-81_110-74del		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 10524 AN: 107112 Hom.: 445 Cov.: 18

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0776

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0574

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0463

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0986

GnomAD4 exome AF: 0.0468 AC: 37040 AN: 791102 Hom.: 765 AF XY: 0.0484 AC XY: 19742 AN XY: 407726

Gnomad4 AFR exome AF: 0.0951

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0337

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.0738

Gnomad4 FIN exome AF: 0.0301

Gnomad4 NFE exome AF: 0.0408

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0983 AC: 10536 AN: 107198 Hom.: 445 Cov.: 18 AF XY: 0.0986 AC XY: 5108 AN XY: 51812

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0574

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0738

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0685 Hom.: 0

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 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879204348; hg19: chr8-1806041;