Variant rs17595424 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_000671.4(ADH5):c.962-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 1,597,514 control chromosomes in the GnomAD database, including 7,401 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.084 ( 574 hom., cov: 33)

Exomes 𝑓: 0.091 ( 6827 hom. )

Consequence

ADH5
NM_000671.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008288

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.333

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

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/exons	MANE	UniProt
ADH5	NM_000671.4 linkuse as main transcript	c.962-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000296412.14

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ADH5	ENST00000296412.14 linkuse as main transcript	c.962-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_000671.4	P1
ADH5	ENST00000626055.2 linkuse as main transcript	c.*649-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5
ADH5	ENST00000512621.5 linkuse as main transcript	n.950-7C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0842

AC:

12796

AN:

152060

Hom.:

574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0858

Gnomad ASJ

AF:

0.0862

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.0447

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0998

GnomAD3 exomes

AF:

0.0745

AC:

17515

AN:

235164

Hom.:

808

AF XY:

0.0749

AC XY:

9539

AN XY:

127398

show subpopulations

Gnomad AFR exome

AF:

0.0806

Gnomad AMR exome

AF:

0.0574

Gnomad ASJ exome

AF:

0.0913

Gnomad EAS exome

AF:

0.000461

Gnomad SAS exome

AF:

0.0341

Gnomad FIN exome

AF:

0.0495

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0901

GnomAD4 exome

AF:

0.0914

AC:

132137

AN:

1445336

Hom.:

6827

Cov.:

AF XY:

0.0904

AC XY:

64911

AN XY:

718340

show subpopulations

Gnomad4 AFR exome

AF:

0.0811

Gnomad4 AMR exome

AF:

0.0600

Gnomad4 ASJ exome

AF:

0.0886

Gnomad4 EAS exome

AF:

0.000304

Gnomad4 SAS exome

AF:

0.0347

Gnomad4 FIN exome

AF:

0.0507

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.0917

GnomAD4 genome

AF:

0.0841

AC:

12804

AN:

152178

Hom.:

574

Cov.:

AF XY:

0.0792

AC XY:

5894

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0830

Gnomad4 AMR

AF:

0.0857

Gnomad4 ASJ

AF:

0.0862

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0349

Gnomad4 FIN

AF:

0.0447

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.0988

Alfa

AF:

0.0992

Hom.:

1005

Bravo

AF:

0.0880

Asia WGS

AF:

0.0210

AC:

AN:

3476

EpiCase

AF:

0.105

EpiControl

AF:

0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.7

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00083

dbscSNV1_RF

Benign

0.060

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over