8-1857879-GATCT-G

Variant names:

• chr8-1857879-GATCT-G
• rs35698984
• NM_014629.4:c.38-36_38-33delATCT

Variant summary

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

The NM_014629.4(ARHGEF10):​c.38-36_38-33delATCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 592,244 control chromosomes in the GnomAD database, including 1,996 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (332 hom., cov: 24)
  • Exomes 𝑓: 0.095 (1664 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.185

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]

KBTBD11-OT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-1857879-GATCT-G is Benign according to our data. Variant chr8-1857879-GATCT-G is described in ClinVar as [Benign]. Clinvar id is 1296031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.38-36_38-33delATCT		intron_variant	Intron 2 of 28	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.38-80_38-77delATCT		intron_variant	Intron 2 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.628-80_628-77delATCT		intron_variant	Intron 3 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 9153 AN: 113478 Hom.: 332 Cov.: 24

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.0106

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0948 AC: 45382 AN: 478694 Hom.: 1664 AF XY: 0.0961 AC XY: 24410 AN XY: 254030

Gnomad4 AFR exome AF: 0.0409

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0306

Gnomad4 SAS exome AF: 0.0932

Gnomad4 FIN exome AF: 0.0885

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0965

GnomAD4 genome AF: 0.0806 AC: 9155 AN: 113550 Hom.: 332 Cov.: 24 AF XY: 0.0796 AC XY: 4385 AN XY: 55056

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.0661

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0517

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0994

Bravo AF: 0.0593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs35698984; hg19: chr8-1806045;