dbSNP rs11568816: ADH5:c.-72C>T (chr4-99088772-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000671.4(ADH5):c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,368,748 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00027 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

ADH5
NM_000671.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.475

Publications

3 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:

ENSG00000246090 (HGNC:):

ENSG00000246090 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4 link	c.-72C>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000296412.14	NP_000662.3	P11766Q6IRT1
LOC100507053	NR_037884.1 link	n.-85G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14 link	c.-72C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_000671.4	ENSP00000296412.8		P11766

Frequencies

GnomAD3 genomes

AF:

0.000272

AC:

AN:

147322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000294

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000524

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000391

AC:

478

AN:

1221320

Hom.:

Cov.:

AF XY:

0.000374

AC XY:

228

AN XY:

610110

show subpopulations

African (AFR)

AF:

0.0000365

AC:

AN:

27398

American (AMR)

AF:

0.00

AC:

AN:

30386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20010

East Asian (EAS)

AF:

0.00

AC:

AN:

33328

South Asian (SAS)

AF:

0.00

AC:

AN:

69018

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

46078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4962

European-Non Finnish (NFE)

AF:

0.000460

AC:

432

AN:

939354

Other (OTH)

AF:

0.000630

AC:

AN:

50786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000271

AC:

AN:

147428

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

71732

show subpopulations

African (AFR)

AF:

0.0000501

AC:

AN:

39882

American (AMR)

AF:

0.00

AC:

AN:

14942

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

4712

South Asian (SAS)

AF:

0.00

AC:

AN:

4342

European-Finnish (FIN)

AF:

0.000294

AC:

AN:

10204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000524

AC:

AN:

66744

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000232

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.3

(source)

DANN

Benign

0.80

PhyloP100

0.47

PromoterAI

-0.29

Neutral

(source)

Splicing

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