4-99124349-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000670.5(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_000670.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH4	NM_000670.5	c.*93A>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.*93A>C		3_prime_UTR_variant	Exon 10 of 10		NP_001293100.1
ADH4	NM_001306172.2	c.*93A>C		3_prime_UTR_variant	Exon 10 of 10		NP_001293101.1
LOC100507053	NR_037884.1	n.429-9206T>G		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512	c.*93A>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_000670.5	ENSP00000265512.7

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

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.829

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.859

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.735

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

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.763

Alfa AF: 0.732 Hom.: 44116

Bravo AF: 0.796

Asia WGS AF: 0.931 AC: 3232 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	11
DANN	Benign	0.89

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

Other links and lift over

dbSNP: rs1042365; hg19: chr4-100045500;