rs13279485

chr8-1935186-T-Cchr8-1935186-T-G

Variant summary

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

The NM_014629.4(ARHGEF10):c.3222+1244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,192 control chromosomes in the GnomAD database, including 343 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 0.060 (343 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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]

LOC100131395 (HGNC:):

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 = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.3222+1244T>C		intron_variant		ENST00000349830.8
LOC100131395	XR_110093.6	n.7585A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.3222+1244T>C		intron_variant		1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9089 AN: 152074 Hom.: 343 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.0593

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

GnomAD4 genome AF: 0.0598 AC: 9095 AN: 152192 Hom.: 343 Cov.: 32 AF XY: 0.0588 AC XY: 4373 AN XY: 74406

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0670

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0902

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0688 Hom.: 229

Bravo AF: 0.0538

Asia WGS AF: 0.0280 AC: 96 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	0.31
Dann	Benign	0.60

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: rs13279485; hg19: chr8-1883352;