rs1042365

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-99124349-T-A
• chr4-99124349-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000670.5(ADH4):​c.*93A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 723,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ADH4 NM_000670.5 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	NM_000670.5	MANE Select	c.*93A>T		3_prime_UTR	Exon 9 of 9	NP_000661.2	P08319-1
	ADH4	NM_001306171.2		c.*93A>T		3_prime_UTR	Exon 10 of 10	NP_001293100.1	P08319-2
	ADH4	NM_001306172.2		c.*93A>T		3_prime_UTR	Exon 10 of 10	NP_001293101.1	P08319-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.*93A>T		3_prime_UTR	Exon 9 of 9	ENSP00000265512.7	P08319-1
	ENSG00000246090	ENST00000500358.6	TSL:1	n.429-9206T>A		intron	N/A
	ADH4	ENST00000508393.5	TSL:2	c.*93A>T		3_prime_UTR	Exon 10 of 10	ENSP00000424630.1	P08319-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000111 AC: 8 AN: 723698 Hom.: 0 Cov.: 9 AF XY: 0.0000105 AC XY: 4 AN XY: 380550

African (AFR) AF: 0.00 AC: 0 AN: 16622

American (AMR) AF: 0.00 AC: 0 AN: 26686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20274

East Asian (EAS) AF: 0.0000609 AC: 2 AN: 32840

South Asian (SAS) AF: 0.00 AC: 0 AN: 55964

European-Finnish (FIN) AF: 0.0000599 AC: 3 AN: 50092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3486

European-Non Finnish (NFE) AF: 0.00000622 AC: 3 AN: 482538

Other (OTH) AF: 0.00 AC: 0 AN: 35196

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 66160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		2.8

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;