8-1892531-G-T

Position:

• chr8-1892531-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):​c.1183-1038G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,884 control chromosomes in the GnomAD database, including 40,414 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40414 hom., cov: 30)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.1183-1038G>T		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.1183-1038G>T		intron_variant		1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*1137-1038G>T		intron_variant		5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109198 AN: 151766 Hom.: 40357 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109318 AN: 151884 Hom.: 40414 Cov.: 30 AF XY: 0.726 AC XY: 53859 AN XY: 74214

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.680

Alfa AF: 0.630 Hom.: 44396

Bravo AF: 0.726

Asia WGS AF: 0.882 AC: 3064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.65

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: rs4242520; hg19: chr8-1840697;