chr4-99311721-A-G

Variant names:

• chr4-99311721-A-G
• rs1229985
• NM_000668.6:c.829-65T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000668.6. 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
	ADH1B	NM_000668.6	MANE Select	c.829-65T>C		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.709-65T>C		intron	N/A	NP_001273579.1	D6RHZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.829-65T>C		intron	N/A	ENSP00000306606.8	P00325-1
	ADH1B	ENST00000625860.2	TSL:1	c.709-65T>C		intron	N/A	ENSP00000486614.1	P00325-2
	ADH1B	ENST00000881106.1		c.829-65T>C		intron	N/A	ENSP00000551165.1

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

African (AFR) AF: 0.0467 AC: 1539 AN: 32924

American (AMR) AF: 0.0769 AC: 3343 AN: 43496

Ashkenazi Jewish (ASJ) AF: 0.0419 AC: 1016 AN: 24228

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39558

South Asian (SAS) AF: 0.0546 AC: 4388 AN: 80384

European-Finnish (FIN) AF: 0.0642 AC: 3335 AN: 51922

Middle Eastern (MID) AF: 0.0307 AC: 127 AN: 4132

European-Non Finnish (NFE) AF: 0.0336 AC: 36665 AN: 1091684

Other (OTH) AF: 0.0366 AC: 2161 AN: 59032

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

African (AFR) AF: 0.0441 AC: 1832 AN: 41536

American (AMR) AF: 0.0521 AC: 797 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 150 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5182

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4828

European-Finnish (FIN) AF: 0.0600 AC: 637 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0354 AC: 2407 AN: 68038

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0368 Hom.: 108

Bravo AF: 0.0417

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.32
PhyloP100		0.34
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: rs1229985; hg19: chr4-100232878;