8-1857879-G-GATCT

Variant names:

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

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_38-33dupATCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 593,336 control chromosomes in the GnomAD database, including 930 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (307 hom., cov: 24)
  • Exomes 𝑓: 0.068 (623 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.397

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-G-GATCT is Benign according to our data. Variant chr8-1857879-G-GATCT is described in ClinVar as [Benign]. Clinvar id is 1234829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.38-36_38-33dupATCT		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.38-81_38-80insATCT		intron_variant	Intron 2 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.628-81_628-80insATCT		intron_variant	Intron 3 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 8851 AN: 113496 Hom.: 307 Cov.: 24

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0856

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.0845

GnomAD4 exome AF: 0.0680 AC: 32607 AN: 479768 Hom.: 623 AF XY: 0.0674 AC XY: 17148 AN XY: 254606

Gnomad4 AFR exome AF: 0.0787

Gnomad4 AMR exome AF: 0.0445

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0460

Gnomad4 FIN exome AF: 0.0343

Gnomad4 NFE exome AF: 0.0675

Gnomad4 OTH exome AF: 0.0823

GnomAD4 genome AF: 0.0780 AC: 8862 AN: 113568 Hom.: 307 Cov.: 24 AF XY: 0.0770 AC XY: 4243 AN XY: 55070

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.0565

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.0839

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs35698984; hg19: chr8-1806045;