8-1857870-AGATC-A

Position:

• chr8-1857870-AGATC-A

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_38-78delGATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 901,120 control chromosomes in the GnomAD database, including 44,185 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5754 hom., cov: 14)
  • Exomes 𝑓: 0.29 (38431 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.624

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 8-1857870-AGATC-A is Benign according to our data. Variant chr8-1857870-AGATC-A is described in ClinVar as [Benign]. Clinvar id is 1292883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.38-81_38-78delGATC		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.38-89_38-86delGATC		intron_variant		1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.628-89_628-86delGATC		intron_variant		5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 40601 AN: 148860 Hom.: 5751 Cov.: 14

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.287 AC: 216121 AN: 752154 Hom.: 38431 AF XY: 0.284 AC XY: 110508 AN XY: 389750

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.273 AC: 40632 AN: 148966 Hom.: 5754 Cov.: 14 AF XY: 0.277 AC XY: 20136 AN XY: 72624

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.265

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

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: rs66620071; hg19: chr8-1806036;