NM_014629.4:c.38-82_38-81insTATCTATCTATC

Variant names:

• chr8-1857875-G-GATCTATCTATCT
• rs35711467
• NM_014629.4:c.38-82_38-81insTATCTATCTATC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014629.4(ARHGEF10):​c.38-82_38-81insTATCTATCTATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 918,338 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0065 (6 hom., cov: 21)
  • Exomes 𝑓: 0.0033 (7 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 695 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 693 AN: 107316 Hom.: 6 Cov.: 21

Gnomad AFR AF: 0.00316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00450

Gnomad ASJ AF: 0.00349

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.00676

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00814

Gnomad OTH AF: 0.00204

GnomAD4 exome AF: 0.00334 AC: 2711 AN: 810934 Hom.: 7 AF XY: 0.00339 AC XY: 1418 AN XY: 418166

Gnomad4 AFR exome AF: 0.00198

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.00623

Gnomad4 SAS exome AF: 0.00357

Gnomad4 FIN exome AF: 0.00886

Gnomad4 NFE exome AF: 0.00289

Gnomad4 OTH exome AF: 0.00367

GnomAD4 genome AF: 0.00647 AC: 695 AN: 107404 Hom.: 6 Cov.: 21 AF XY: 0.00653 AC XY: 339 AN XY: 51920

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.00450

Gnomad4 ASJ AF: 0.00349

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.00814

Gnomad4 OTH AF: 0.00202

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;