rs14375

Positions:

• chr8-1958464-G-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.*1201G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,252 control chromosomes in the GnomAD database, including 66,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.93 (66556 hom., cov: 32)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: ARHGEF10 NM_014629.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-1958464-G-T is Benign according to our data. Variant chr8-1958464-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.*1201G>T		3_prime_UTR_variant	29/29	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.*1201G>T		3_prime_UTR_variant	29/29	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*5190G>T		non_coding_transcript_exon_variant	30/30	5		ENSP00000489726.1
KBTBD11-OT1	ENST00000635855.1	n.*5190G>T		3_prime_UTR_variant	30/30	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142198 AN: 152126 Hom.: 66496 Cov.: 32

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.919

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.935 AC: 142317 AN: 152244 Hom.: 66556 Cov.: 32 AF XY: 0.938 AC XY: 69831 AN XY: 74438

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.920

Alfa AF: 0.932 Hom.: 90721

Bravo AF: 0.930

Asia WGS AF: 0.985 AC: 3426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.51

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: rs14375; hg19: chr8-1906630;