rs3751082

Positions:

• chr11-68027885-G-A
• chr11-68027885-G-C

Variant summary

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

The NM_000694.4(ALDH3B1):​c.1353G>A​(p.Leu451Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,563,316 control chromosomes in the GnomAD database, including 30,395 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 0.19 (3016 hom., cov: 33)
  • Exomes 𝑓: 0.20 (27379 hom.)
• Consequence: ALDH3B1 NM_000694.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

Genes affected

ALDH3B1 (HGNC:410): (aldehyde dehydrogenase 3 family member B1) This gene encodes a member of the aldehyde dehydrogenase protein family. Aldehyde dehydrogenases are a family of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The encoded protein is able to oxidize long-chain fatty aldehydes in vitro, and may play a role in protection from oxidative stress. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ALDH3B1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=0.624 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B1	NM_000694.4	c.1353G>A	p.Leu451Leu	synonymous_variant	10/10	ENST00000342456.11	NP_000685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3B1	ENST00000342456.11	c.1353G>A	p.Leu451Leu	synonymous_variant	10/10	1	NM_000694.4	ENSP00000473990.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29526 AN: 152062 Hom.: 3003 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.208 AC: 33936 AN: 163536 Hom.: 3484 AF XY: 0.205 AC XY: 18084 AN XY: 88070

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.246

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.195 AC: 275290 AN: 1411136 Hom.: 27379 Cov.: 33 AF XY: 0.194 AC XY: 135407 AN XY: 697882

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.194 AC: 29577 AN: 152180 Hom.: 3016 Cov.: 33 AF XY: 0.198 AC XY: 14745 AN XY: 74392

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.171

Alfa AF: 0.188 Hom.: 2618

Bravo AF: 0.184

Asia WGS AF: 0.190 AC: 657 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.89

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: rs3751082; hg19: chr11-67795353; COSMIC: COSV50288790; COSMIC: COSV50288790;