4-99124423-T-C

Variant names:

• chr4-99124423-T-C
• rs1042364
• NM_000670.5:c.*19A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 28 publications found

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]

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	NM_000670.5	MANE Select	c.*19A>G		3_prime_UTR	Exon 9 of 9	NP_000661.2
	ADH4	NM_001306171.2		c.*19A>G		3_prime_UTR	Exon 10 of 10	NP_001293100.1
	ADH4	NM_001306172.2		c.*19A>G		3_prime_UTR	Exon 10 of 10	NP_001293101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.*19A>G		3_prime_UTR	Exon 9 of 9	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.429-9132T>C		intron	N/A
	ADH4	ENST00000509471.5	TSL:3	n.*168A>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000424583.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119970 AN: 152018 Hom.: 48014 Cov.: 32

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

GnomAD2 exomes AF: 0.785 AC: 182653 AN: 232700 AF XY: 0.779

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 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.: 23 AF XY: 0.739 AC XY: 484269 AN XY: 655170

African (AFR) AF: 0.893 AC: 26478 AN: 29662

American (AMR) AF: 0.852 AC: 35394 AN: 41518

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 17221 AN: 24956

East Asian (EAS) AF: 0.998 AC: 37632 AN: 37690

South Asian (SAS) AF: 0.864 AC: 66525 AN: 77030

European-Finnish (FIN) AF: 0.758 AC: 40040 AN: 52798

Middle Eastern (MID) AF: 0.751 AC: 3962 AN: 5278

European-Non Finnish (NFE) AF: 0.706 AC: 694280 AN: 983266

Other (OTH) AF: 0.748 AC: 41100 AN: 54926

GnomAD4 genome AF: 0.789 AC: 120085 AN: 152136 Hom.: 48068 Cov.: 32 AF XY: 0.797 AC XY: 59253 AN XY: 74358

African (AFR) AF: 0.891 AC: 36975 AN: 41518

American (AMR) AF: 0.792 AC: 12100 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2434 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5165 AN: 5174

South Asian (SAS) AF: 0.883 AC: 4260 AN: 4822

European-Finnish (FIN) AF: 0.767 AC: 8088 AN: 10550

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48626 AN: 68010

Other (OTH) AF: 0.763 AC: 1609 AN: 2110

Alfa AF: 0.742 Hom.: 95795

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.69
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	9.3e-7	T
PhyloP100		0.50
Vest4		0.11
GERP RS		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042364; hg19: chr4-100045574;