8-1857875-G-GATCTATCT

Variant names:

• chr8-1857875-G-GATCTATCT
• rs35711467
• NM_014629.4:c.38-82_38-81insTATCTATC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014629.4(ARHGEF10):​c.38-82_38-81insTATCTATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 917,620 control chromosomes in the GnomAD database, including 170 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (51 hom., cov: 21)
  • Exomes 𝑓: 0.016 (119 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0302 (3247/107350) while in subpopulation EAS AF= 0.0422 (147/3486). AF 95% confidence interval is 0.0366. There are 51 homozygotes in gnomad4. There are 1573 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.38-82_38-81insTATCTATC		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.38-85_38-84insATCTATCT		intron_variant	Intron 2 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.628-85_628-84insATCTATCT		intron_variant	Intron 3 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 3246 AN: 107262 Hom.: 50 Cov.: 21

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0421

Gnomad SAS AF: 0.0380

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0180

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.0165 AC: 13332 AN: 810270 Hom.: 119 AF XY: 0.0171 AC XY: 7150 AN XY: 417828

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.0138

Gnomad4 ASJ exome AF: 0.0154

Gnomad4 EAS exome AF: 0.0347

Gnomad4 SAS exome AF: 0.0245

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0302 AC: 3247 AN: 107350 Hom.: 51 Cov.: 21 AF XY: 0.0303 AC XY: 1573 AN XY: 51892

Gnomad4 AFR AF: 0.0234

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.0379

Gnomad4 FIN AF: 0.0290

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0216

ClinVar

Not reported in ClinVar

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: rs35711467; hg19: chr8-1806041;