rs6991392

Positions:

• chr8-1957657-A-G
• chr8-1957657-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_014629.4(ARHGEF10):​c.*394A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 197,908 control chromosomes in the GnomAD database, including 14,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.37 (10642 hom., cov: 34)
  • Exomes 𝑓: 0.40 (3507 hom.)
• Consequence: ARHGEF10 NM_014629.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-1957657-A-G is Benign according to our data. Variant chr8-1957657-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGEF10	NM_014629.4	c.*394A>G		3_prime_UTR_variant	29/29	ENST00000349830.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.*394A>G		3_prime_UTR_variant	29/29	1	NM_014629.4	P4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56238 AN: 151976 Hom.: 10640 Cov.: 34

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.404 AC: 18503 AN: 45812 Hom.: 3507 Cov.: 0 AF XY: 0.406 AC XY: 9546 AN XY: 23532

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.586

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.394

GnomAD4 genome AF: 0.370 AC: 56252 AN: 152096 Hom.: 10642 Cov.: 34 AF XY: 0.372 AC XY: 27687 AN XY: 74354

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.394

Alfa AF: 0.377 Hom.: 14621

Bravo AF: 0.364

Asia WGS AF: 0.519 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.35

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: rs6991392; hg19: chr8-1905823;