rs12507573

Variant names:

• chr4-99305167-C-A
• rs12507573
• ENST00000305046:c.*2673G>T

Variant summary

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

The NM_000668.6(ADH1B):​c.*2673G>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 0.436 in 151,158 control chromosomes in the GnomAD database, including 14,824 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 0.44 (14824 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: ADH1B NM_000668.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

ADH1B (HGNC:250): (alcohol dehydrogenase 1B (class I), beta polypeptide) The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.*2673G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.*2673G>T		3_prime_UTR_variant	Exon 10 of 10		NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046	c.*2673G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000668.6	ENSP00000306606.8
ADH1B	ENST00000625860	c.*2673G>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000486614.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 65887 AN: 151040 Hom.: 14809 Cov.: 28

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.466

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.436 AC: 65941 AN: 151158 Hom.: 14824 Cov.: 28 AF XY: 0.432 AC XY: 31899 AN XY: 73790

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.464

Alfa AF: 0.448 Hom.: 2642

Bravo AF: 0.441

Asia WGS AF: 0.233 AC: 810 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.12

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: rs12507573; hg19: chr4-100226324;