rs308335

Positions:

• chr11-68009216-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161473.3(ALDH3B1):​c.-2+524A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 152,302 control chromosomes in the GnomAD database, including 546 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 0.050 (546 hom., cov: 33)
• Consequence: ALDH3B1 NM_001161473.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH3B1	NM_001161473.3	c.-2+524A>G		intron_variant			NP_001154945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH3B1	ENST00000614849.4	c.-2+524A>G		intron_variant		1		ENSP00000478486.1

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7574 AN: 152184 Hom.: 543 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00434

Gnomad OTH AF: 0.0311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0498 AC: 7589 AN: 152302 Hom.: 546 Cov.: 33 AF XY: 0.0493 AC XY: 3670 AN XY: 74488

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.0744

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00434

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0243 Hom.: 65

Bravo AF: 0.0555

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.31

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: rs308335; hg19: chr11-67776686;