Variant rs1126672 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000670.5(ADH4):c.1051C>T(p.Leu351=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,610,126 control chromosomes in the GnomAD database, including 53,540 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 0.21 ( 4047 hom., cov: 32)

Exomes 𝑓: 0.25 ( 49493 hom. )

Consequence

ADH4
NM_000670.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210

Variant links:

Genes affected

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which 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. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

ADH4 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=0.021 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADH4	NM_000670.5 linkuse as main transcript	c.1051C>T	p.Leu351=	synonymous_variant	8/9	ENST00000265512.12
LOC100507053	NR_037884.1 linkuse as main transcript	n.429-6894G>A		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2 linkuse as main transcript	c.1108C>T	p.Leu370=	synonymous_variant	9/10
ADH4	NM_001306172.2 linkuse as main transcript	c.1108C>T	p.Leu370=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH4	ENST00000265512.12 linkuse as main transcript	c.1051C>T	p.Leu351=	synonymous_variant	8/9	1	NM_000670.5	P1	P08319-1
	ENST00000500358.6 linkuse as main transcript	n.429-6894G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32040

AN:

152042

Hom.:

4050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.299

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.240

GnomAD3 exomes

AF:

0.208

AC:

52179

AN:

251012

Hom.:

6683

AF XY:

0.214

AC XY:

28968

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.251

AC:

365928

AN:

1457966

Hom.:

49493

Cov.:

AF XY:

0.249

AC XY:

180803

AN XY:

725252

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.00154

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.211

AC:

32041

AN:

152160

Hom.:

4047

Cov.:

AF XY:

0.203

AC XY:

15096

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.299

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.238

Alfa

AF:

0.268

Hom.:

13641

Bravo

AF:

0.204

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.44

DANN

Benign

0.60

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

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