Genetic Variant NM_000668.6:c.829-65T>C (chr4-99311721-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

Publications

5 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1B	NM_000668.6 link	c.829-65T>C		intron_variant	Intron 6 of 8	ENST00000305046.13	NP_000659.2	P00325-1V9HW50
ADH1B	NM_001286650.2 link	c.709-65T>C		intron_variant	Intron 7 of 9		NP_001273579.1	P00325-2D6RHZ6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADH1B	ENST00000305046.13 link	c.829-65T>C	intron_variant	Intron 6 of 8	1	NM_000668.6	ENSP00000306606.8	P00325-1
ADH1B	ENST00000625860.2 link	c.709-65T>C	intron_variant	Intron 6 of 8	1		ENSP00000486614.1	P00325-2D6RHZ6
ADH1B	ENST00000506651.5 link	c.709-65T>C	intron_variant	Intron 7 of 9	2		ENSP00000425998.2	P00325-2D6RHZ6
ADH1B	ENST00000515694.4 link	n.2924-65T>C	intron_variant	Intron 6 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6231

AN:

152170

Hom.:

142

Cov.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2580

5160

7741

10321

12901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1398

2796

4194

5592

6990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0409

AC:

6236

AN:

152288

Hom.:

142

Cov.:

AF XY:

0.0419

AC XY:

3119

AN XY:

74476

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0354

AC:

2407

AN:

68038

Other (OTH)

AF:

0.0374

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

325

650

976

1301

1626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

(source)

DANN

Benign

0.32

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over