NM_000668.6:c.964+78A>G

Variant names:

• chr4-99311443-T-C
• rs17028834
• NM_000668.6:c.964+78A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000668.6(ADH1B):​c.964+78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00749 in 1,475,662 control chromosomes in the GnomAD database, including 564 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 0.036 (293 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (271 hom.)
• Consequence: ADH1B NM_000668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• 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 (AFR) allele frequency at 95% confidence interval = 0.119 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.964+78A>G		intron	N/A	NP_000659.2
	ADH1B	NM_001286650.2		c.844+78A>G		intron	N/A	NP_001273579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.964+78A>G		intron	N/A	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.844+78A>G		intron	N/A	ENSP00000486614.1
	ADH1B	ENST00000506651.5	TSL:2	c.844+78A>G		intron	N/A	ENSP00000425998.2

Frequencies

GnomAD3 genomes AF: 0.0355 AC: 5401 AN: 152148 Hom.: 290 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00426 AC: 5639 AN: 1323396 Hom.: 271 AF XY: 0.00385 AC XY: 2527 AN XY: 656702

African (AFR) AF: 0.127 AC: 3750 AN: 29624

American (AMR) AF: 0.00912 AC: 308 AN: 33788

Ashkenazi Jewish (ASJ) AF: 0.00279 AC: 61 AN: 21886

East Asian (EAS) AF: 0.00 AC: 0 AN: 38868

South Asian (SAS) AF: 0.000980 AC: 69 AN: 70416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50540

Middle Eastern (MID) AF: 0.0139 AC: 74 AN: 5324

European-Non Finnish (NFE) AF: 0.000864 AC: 879 AN: 1017850

Other (OTH) AF: 0.00904 AC: 498 AN: 55100

GnomAD4 genome AF: 0.0356 AC: 5419 AN: 152266 Hom.: 293 Cov.: 32 AF XY: 0.0351 AC XY: 2612 AN XY: 74460

African (AFR) AF: 0.121 AC: 5041 AN: 41514

American (AMR) AF: 0.0141 AC: 216 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000956 AC: 65 AN: 68024

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.00962 Hom.: 111

Bravo AF: 0.0404

Asia WGS AF: 0.00953 AC: 34 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	4.1
DANN	Benign	0.54
PhyloP100		0.055
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: rs17028834; hg19: chr4-100232600;