rs6558551

Variant names:

• chr8-1834329-G-A
• rs6558551
• NM_014629.4:c.-47-9024G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-1834329-G-A
• chr8-1834329-G-C
• chr8-1834329-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014629.4(ARHGEF10):​c.-47-9024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,952 control chromosomes in the GnomAD database, including 26,946 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 0.59 (26946 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 5 publications found

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]

ARHGEF10 Gene-Disease associations (from GenCC):

• autosomal dominant slowed nerve conduction velocity

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• hereditary peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KBTBD11-OT1 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.-47-9024G>A		intron_variant	Intron 1 of 28	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.-47-9024G>A		intron_variant	Intron 1 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.544-9024G>A		intron_variant	Intron 2 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89856 AN: 151834 Hom.: 26940 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.592 AC: 89885 AN: 151952 Hom.: 26946 Cov.: 32 AF XY: 0.582 AC XY: 43201 AN XY: 74264

African (AFR) AF: 0.574 AC: 23776 AN: 41436

American (AMR) AF: 0.554 AC: 8469 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1886 AN: 5148

South Asian (SAS) AF: 0.501 AC: 2409 AN: 4810

European-Finnish (FIN) AF: 0.540 AC: 5702 AN: 10552

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43040 AN: 67938

Other (OTH) AF: 0.622 AC: 1315 AN: 2114

Alfa AF: 0.622 Hom.: 79227

Bravo AF: 0.591

Asia WGS AF: 0.399 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.43
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6558551; hg19: chr8-1782495;