rs4242548

Positions:

• chr8-1932364-T-C

Variant summary

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

The NM_014629.4(ARHGEF10):​c.3080-1436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,130 control chromosomes in the GnomAD database, including 15,883 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 0.45 (15883 hom., cov: 34)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.3080-1436T>C		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3080-1436T>C		intron_variant		1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*3034-1436T>C		intron_variant		5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67854 AN: 152012 Hom.: 15867 Cov.: 34

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.446 AC: 67906 AN: 152130 Hom.: 15883 Cov.: 34 AF XY: 0.456 AC XY: 33943 AN XY: 74378

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.447

Alfa AF: 0.455 Hom.: 15930

Bravo AF: 0.434

Asia WGS AF: 0.696 AC: 2420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.66

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: rs4242548; hg19: chr8-1880530;