4-99124349-T-G

Variant names:

• chr4-99124349-T-G
• rs1042365
• NM_000670.5:c.*93A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001306171.2(ADH4):​c.*93A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 871,058 control chromosomes in the GnomAD database, including 239,110 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 (48032 hom., cov: 32)
  • Exomes 𝑓: 0.72 (191078 hom.)
• Consequence: ADH4 NM_001306171.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77
• Publications: 13 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• 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_001306171.2. 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.*93A>C		3_prime_UTR	Exon 9 of 9	NP_000661.2
	ADH4	NM_001306171.2		c.*93A>C		3_prime_UTR	Exon 10 of 10	NP_001293100.1
	ADH4	NM_001306172.2		c.*93A>C		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.*93A>C		3_prime_UTR	Exon 9 of 9	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.429-9206T>G		intron	N/A
	ADH4	ENST00000508393.5	TSL:2	c.*93A>C		3_prime_UTR	Exon 10 of 10	ENSP00000424630.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119885 AN: 151926 Hom.: 47978 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.760

GnomAD4 exome AF: 0.722 AC: 519164 AN: 719014 Hom.: 191078 Cov.: 9 AF XY: 0.726 AC XY: 274701 AN XY: 378124

African (AFR) AF: 0.878 AC: 14544 AN: 16564

American (AMR) AF: 0.829 AC: 22013 AN: 26566

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 13791 AN: 20186

East Asian (EAS) AF: 0.998 AC: 32788 AN: 32840

South Asian (SAS) AF: 0.859 AC: 47995 AN: 55850

European-Finnish (FIN) AF: 0.758 AC: 37842 AN: 49952

Middle Eastern (MID) AF: 0.743 AC: 2579 AN: 3470

European-Non Finnish (NFE) AF: 0.673 AC: 321887 AN: 478594

Other (OTH) AF: 0.735 AC: 25725 AN: 34992

GnomAD4 genome AF: 0.789 AC: 120000 AN: 152044 Hom.: 48032 Cov.: 32 AF XY: 0.797 AC XY: 59189 AN XY: 74286

African (AFR) AF: 0.890 AC: 36946 AN: 41494

American (AMR) AF: 0.792 AC: 12093 AN: 15274

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

East Asian (EAS) AF: 0.998 AC: 5163 AN: 5172

South Asian (SAS) AF: 0.884 AC: 4245 AN: 4802

European-Finnish (FIN) AF: 0.766 AC: 8072 AN: 10536

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

European-Non Finnish (NFE) AF: 0.715 AC: 48608 AN: 67976

Other (OTH) AF: 0.763 AC: 1611 AN: 2112

Alfa AF: 0.745 Hom.: 66160

Bravo AF: 0.796

Asia WGS AF: 0.931 AC: 3232 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		2.8
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: rs1042365; hg19: chr4-100045500;