Genetic Variant ADH5:c.*417G>A (chr4-99072000-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000671.4(ADH5):c.*417G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 165,838 control chromosomes in the GnomAD database, including 592 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 0.082 ( 544 hom., cov: 32)

Exomes 𝑓: 0.078 ( 48 hom. )

Consequence

ADH5
NM_000671.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

16 publications found

Variant links:

Genes affected

ADH5 (HGNC:253): (alcohol dehydrogenase 5 (class III), chi polypeptide) This gene encodes a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene. [provided by RefSeq, Oct 2008]

ADH5 Gene-Disease associations (from GenCC):

AMED syndrome, digenic
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ADH5 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4 link	c.*417G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000296412.14	NP_000662.3	P11766Q6IRT1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADH5	ENST00000296412.14 link	c.*417G>A	3_prime_UTR_variant	Exon 9 of 9	1	NM_000671.4	ENSP00000296412.8	P11766
ADH5	ENST00000626055.2 link	c.*1229G>A	downstream_gene_variant		5		ENSP00000487496.1	D6RAY0
ADH5	ENST00000512621.5 link	n.*186G>A	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0817

AC:

12424

AN:

152020

Hom.:

544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0733

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0852

Gnomad ASJ

AF:

0.0894

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.0444

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0982

GnomAD4 exome

AF:

0.0782

AC:

1071

AN:

13700

Hom.:

Cov.:

AF XY:

0.0739

AC XY:

526

AN XY:

7116

show subpopulations

African (AFR)

AF:

0.0829

AC:

AN:

374

American (AMR)

AF:

0.0830

AC:

AN:

578

Ashkenazi Jewish (ASJ)

AF:

0.0907

AC:

AN:

408

East Asian (EAS)

AF:

0.00

AC:

AN:

526

South Asian (SAS)

AF:

0.0293

AC:

AN:

818

European-Finnish (FIN)

AF:

0.0406

AC:

AN:

690

Middle Eastern (MID)

AF:

0.0909

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0890

AC:

840

AN:

9436

Other (OTH)

AF:

0.0714

AC:

AN:

826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0817

AC:

12433

AN:

152138

Hom.:

544

Cov.:

AF XY:

0.0770

AC XY:

5724

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0734

AC:

3047

AN:

41500

American (AMR)

AF:

0.0851

AC:

1300

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0894

AC:

310

AN:

3466

East Asian (EAS)

AF:

0.000387

AC:

AN:

5164

South Asian (SAS)

AF:

0.0350

AC:

169

AN:

4822

European-Finnish (FIN)

AF:

0.0444

AC:

470

AN:

10594

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6847

AN:

67996

Other (OTH)

AF:

0.0972

AC:

205

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

581

1162

1744

2325

2906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0960

Hom.:

2025

Bravo

AF:

0.0855

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.44

(source)

DANN

Benign

0.52

PhyloP100

-1.3

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