rs56151250

Positions:

• chr11-18534354-C-G
• chr11-18534354-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001040697.4(UEVLD):​c.1224G>C​(p.Val408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,540,612 control chromosomes in the GnomAD database, including 27,323 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 0.16 (2581 hom., cov: 32)
  • Exomes 𝑓: 0.17 (24742 hom.)
• Consequence: UEVLD NM_001040697.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535

Genes affected

UEVLD (HGNC:30866): (UEV and lactate/malate dehyrogenase domains) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in several processes, including carbohydrate metabolic process; cellular protein modification process; and protein transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.535 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UEVLD	NM_001040697.4	c.1224G>C	p.Val408=	synonymous_variant	11/12	ENST00000396197.8	NP_001035787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UEVLD	ENST00000396197.8	c.1224G>C	p.Val408=	synonymous_variant	11/12	5	NM_001040697.4	ENSP00000379500	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24405 AN: 152014 Hom.: 2560 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.197 AC: 38804 AN: 196938 Hom.: 4629 AF XY: 0.199 AC XY: 21610 AN XY: 108356

Gnomad AFR exome AF: 0.0604

Gnomad AMR exome AF: 0.234

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.374

Gnomad SAS exome AF: 0.293

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.175 AC: 242923 AN: 1388480 Hom.: 24742 Cov.: 29 AF XY: 0.177 AC XY: 122419 AN XY: 689726

Gnomad4 AFR exome AF: 0.0616

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.446

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.161 AC: 24449 AN: 152132 Hom.: 2581 Cov.: 32 AF XY: 0.173 AC XY: 12852 AN XY: 74356

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.183

Alfa AF: 0.155 Hom.: 694

Bravo AF: 0.148

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.0
DANN	Benign	0.75

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: rs56151250; hg19: chr11-18555901; COSMIC: COSV57874941; COSMIC: COSV57874941;