rs6558551

Positions:

• chr8-1834329-G-A
• chr8-1834329-G-C
• chr8-1834329-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.-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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.-47-9024G>A		intron_variant		ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.-47-9024G>A		intron_variant		1	NM_014629.4	P4
ARHGEF10	ENST00000518288.5	c.25+8194G>A		intron_variant		1
ARHGEF10	ENST00000520359.5	c.-47-9024G>A		intron_variant		1		A2
ARHGEF10	ENST00000398564.5	c.25+8194G>A		intron_variant		5		A2

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

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.622

Alfa AF: 0.629 Hom.: 46270

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6558551; hg19: chr8-1782495;