dbSNP rs4699699: ADH5:c.825+264G>C (chr4-99076028-C-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_000671.4(ADH5):c.825+264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 406,130 control chromosomes in the GnomAD database, including 1,594 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 0.084 ( 577 hom., cov: 32)

Exomes 𝑓: 0.080 ( 1017 hom. )

Consequence

ADH5
NM_000671.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.833

Publications

4 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4 link	c.825+264G>C		intron_variant	Intron 6 of 8	ENST00000296412.14	NP_000662.3	P11766Q6IRT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14 link	c.825+264G>C		intron_variant	Intron 6 of 8	1	NM_000671.4	ENSP00000296412.8		P11766

Frequencies

GnomAD3 genomes

AF:

0.0841

AC:

12795

AN:

152128

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0857

Gnomad ASJ

AF:

0.0861

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0348

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0992

GnomAD4 exome

AF:

0.0800

AC:

20304

AN:

253884

Hom.:

1017

Cov.:

AF XY:

0.0762

AC XY:

10252

AN XY:

134498

show subpopulations

African (AFR)

AF:

0.0800

AC:

618

AN:

7724

American (AMR)

AF:

0.0716

AC:

726

AN:

10134

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

688

AN:

7680

East Asian (EAS)

AF:

0.000207

AC:

AN:

14458

South Asian (SAS)

AF:

0.0335

AC:

1071

AN:

31950

European-Finnish (FIN)

AF:

0.0507

AC:

623

AN:

12288

Middle Eastern (MID)

AF:

0.0833

AC:

AN:

1068

European-Non Finnish (NFE)

AF:

0.0988

AC:

15224

AN:

154146

Other (OTH)

AF:

0.0874

AC:

1262

AN:

14436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

873

1747

2620

3494

4367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0841

AC:

12803

AN:

152246

Hom.:

577

Cov.:

AF XY:

0.0792

AC XY:

5897

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.0829

AC:

3445

AN:

41536

American (AMR)

AF:

0.0856

AC:

1308

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0861

AC:

299

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.0350

AC:

169

AN:

4826

European-Finnish (FIN)

AF:

0.0447

AC:

474

AN:

10612

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6820

AN:

68008

Other (OTH)

AF:

0.0982

AC:

207

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

596

1192

1788

2384

2980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0891

Hom.:

Bravo

AF:

0.0880

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

-0.85

CADD

Benign

0.57

(source)

DANN

Benign

0.43

PhyloP100

-0.83

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