rs1229985

Positions:

• chr4-99311721-A-G

Variant summary

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

The NM_000668.6(ADH1B):​c.829-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,579,648 control chromosomes in the GnomAD database, including 1,330 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 0.041 (142 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1188 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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]

ADH1B (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1B	NM_000668.6	c.829-65T>C		intron_variant		ENST00000305046.13	NP_000659.2
ADH1B	NM_001286650.2	c.709-65T>C		intron_variant			NP_001273579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1B	ENST00000305046.13	c.829-65T>C		intron_variant		1	NM_000668.6	ENSP00000306606.8
ADH1B	ENST00000625860.2	c.709-65T>C		intron_variant		1		ENSP00000486614.1
ADH1B	ENST00000506651.5	c.709-65T>C		intron_variant		2		ENSP00000425998.2
ADH1B	ENST00000515694.4	n.2924-65T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6231 AN: 152170 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0368 AC: 52580 AN: 1427360 Hom.: 1188 AF XY: 0.0372 AC XY: 26367 AN XY: 708662

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.0419

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0546

Gnomad4 FIN exome AF: 0.0642

Gnomad4 NFE exome AF: 0.0336

Gnomad4 OTH exome AF: 0.0366

GnomAD4 genome AF: 0.0409 AC: 6236 AN: 152288 Hom.: 142 Cov.: 32 AF XY: 0.0419 AC XY: 3119 AN XY: 74476

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.0600

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0411 Hom.: 23

Bravo AF: 0.0417

Asia WGS AF: 0.0390 AC: 134 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	0.24
DANN	Benign	0.32

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: rs1229985; hg19: chr4-100232878;