11-68027885-G-A

Variant names:

• chr11-68027885-G-A
• rs3751082
• NM_000694.4:c.1353G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

GLTC1 (HGNC:56861):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B1	NM_000694.4	MANE Select	c.1353G>A	p.Leu451Leu	synonymous	Exon 10 of 10	NP_000685.1	P43353-1
	ALDH3B1	NM_001161473.3		c.1353G>A	p.Leu451Leu	synonymous	Exon 10 of 10	NP_001154945.1	P43353-1
	ALDH3B1	NM_001030010.3		c.1242G>A	p.Leu414Leu	synonymous	Exon 9 of 9	NP_001025181.1	P43353-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B1	ENST00000342456.11	TSL:1 MANE Select	c.1353G>A	p.Leu451Leu	synonymous	Exon 10 of 10	ENSP00000473990.2	P43353-1
	ALDH3B1	ENST00000614849.4	TSL:1	c.1353G>A	p.Leu451Leu	synonymous	Exon 10 of 10	ENSP00000478486.1	P43353-1
	ALDH3B1	ENST00000617288.4	TSL:1	c.1242G>A	p.Leu414Leu	synonymous	Exon 9 of 9	ENSP00000481604.1	P43353-2

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

GnomAD2 exomes AF: 0.208 AC: 33936 AN: 163536 AF XY: 0.205

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 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

African (AFR) AF: 0.166 AC: 5343 AN: 32284

American (AMR) AF: 0.180 AC: 6779 AN: 37748

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4319 AN: 25298

East Asian (EAS) AF: 0.214 AC: 7864 AN: 36802

South Asian (SAS) AF: 0.161 AC: 12914 AN: 80260

European-Finnish (FIN) AF: 0.310 AC: 14186 AN: 45804

Middle Eastern (MID) AF: 0.126 AC: 722 AN: 5716

European-Non Finnish (NFE) AF: 0.194 AC: 211480 AN: 1088602

Other (OTH) AF: 0.199 AC: 11683 AN: 58622

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

African (AFR) AF: 0.170 AC: 7053 AN: 41520

American (AMR) AF: 0.188 AC: 2880 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1183 AN: 5174

South Asian (SAS) AF: 0.161 AC: 775 AN: 4828

European-Finnish (FIN) AF: 0.318 AC: 3368 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13178 AN: 67982

Other (OTH) AF: 0.171 AC: 361 AN: 2110

Alfa AF: 0.188 Hom.: 4274

Bravo AF: 0.184

Asia WGS AF: 0.190 AC: 657 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.89
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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