Variant chr4-99124423-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000670.5(ADH4):c.*19A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,459,260 control chromosomes in the GnomAD database, including 408,810 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 0.79 ( 48068 hom., cov: 32)

Exomes 𝑓: 0.74 ( 360742 hom. )

Consequence

ADH4
NM_000670.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.500

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.252315E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ADH4	NM_000670.5 linkuse as main transcript	c.*19A>G	3_prime_UTR_variant	9/9	ENST00000265512.12
LOC100507053	NR_037884.1 linkuse as main transcript	n.429-9132T>C	intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2 linkuse as main transcript	c.*19A>G	3_prime_UTR_variant	10/10
ADH4	NM_001306172.2 linkuse as main transcript	c.*19A>G	3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH4	ENST00000265512.12 linkuse as main transcript	c.*19A>G		3_prime_UTR_variant	9/9	1	NM_000670.5	P1	P08319-1
	ENST00000500358.6 linkuse as main transcript	n.429-9132T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.789

AC:

119970

AN:

152018

Hom.:

48014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.883

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.760

GnomAD3 exomes

AF:

0.785

AC:

182653

AN:

232700

Hom.:

72918

AF XY:

0.779

AC XY:

97839

AN XY:

125612

show subpopulations

Gnomad AFR exome

AF:

0.892

Gnomad AMR exome

AF:

0.858

Gnomad ASJ exome

AF:

0.698

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.863

Gnomad FIN exome

AF:

0.764

Gnomad NFE exome

AF:

0.709

Gnomad OTH exome

AF:

0.749

GnomAD4 exome

AF:

0.736

AC:

962632

AN:

1307124

Hom.:

360742

Cov.:

AF XY:

0.739

AC XY:

484269

AN XY:

655170

show subpopulations

Gnomad4 AFR exome

AF:

0.893

Gnomad4 AMR exome

AF:

0.852

Gnomad4 ASJ exome

AF:

0.690

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.864

Gnomad4 FIN exome

AF:

0.758

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.789

AC:

120085

AN:

152136

Hom.:

48068

Cov.:

AF XY:

0.797

AC XY:

59253

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.891

Gnomad4 AMR

AF:

0.792

Gnomad4 ASJ

AF:

0.701

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.883

Gnomad4 FIN

AF:

0.767

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.763

Alfa

AF:

0.727

Hom.:

60202

Bravo

AF:

0.796

TwinsUK

AF:

0.716

AC:

2654

ALSPAC

AF:

0.723

AC:

2786

ESP6500AA

AF:

0.890

AC:

3916

ESP6500EA

AF:

0.711

AC:

6113

ExAC

AF:

0.784

AC:

95124

Asia WGS

AF:

0.932

AC:

3237

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.3

DANN

Benign

0.69

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.25

MetaRNN

Benign

9.3e-7

MutationTaster

Benign

0.038

P;P;P;P

Vest4

0.11

GERP RS

2.3

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