8-1857875-G-GATCT

Variant names:

• chr8-1857875-G-GATCT
• rs35711467
• NM_014629.4:c.38-82_38-81insTATC

Variant summary

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

The NM_014629.4(ARHGEF10):​c.38-82_38-81insTATC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 913,524 control chromosomes in the GnomAD database, including 3,602 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (1185 hom., cov: 21)
  • Exomes 𝑓: 0.087 (2417 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 8-1857875-G-GATCT is Benign according to our data. Variant chr8-1857875-G-GATCT is described in ClinVar as [Benign]. Clinvar id is 1229075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.172 AC: 18428 AN: 106964 Hom.: 1185 Cov.: 21

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.0869 AC: 70069 AN: 806472 Hom.: 2417 AF XY: 0.0904 AC XY: 37584 AN XY: 415852

Gnomad4 AFR exome AF: 0.0797

Gnomad4 AMR exome AF: 0.0941

Gnomad4 ASJ exome AF: 0.0522

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0752

Gnomad4 OTH exome AF: 0.0926

GnomAD4 genome AF: 0.172 AC: 18439 AN: 107052 Hom.: 1185 Cov.: 21 AF XY: 0.174 AC XY: 8989 AN XY: 51758

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.140

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: rs35711467; hg19: chr8-1806041;