4-99144442-T-A

Variant names:

• chr4-99144442-T-A
• rs1800761
• ENST00000500358.6:n.680-10103T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000500358.6(ENSG00000246090):​n.680-10103T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 7 publications found

Genes affected

ENSG00000246090 (HGNC:):

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500358.6. 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
	LOC100507053	NR_037884.1		n.680-10103T>A		intron	N/A
	ADH4	NM_000670.5	MANE Select	c.-220A>T		upstream_gene	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.-311A>T		upstream_gene	N/A	NP_001293100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-10103T>A		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-1662A>T		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.676+10637T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 270438 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 139630

African (AFR) AF: 0.00 AC: 0 AN: 7714

American (AMR) AF: 0.00 AC: 0 AN: 9498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9524

East Asian (EAS) AF: 0.00 AC: 0 AN: 24046

South Asian (SAS) AF: 0.00 AC: 0 AN: 9394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 169580

Other (OTH) AF: 0.00 AC: 0 AN: 17218

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		-1.5
PromoterAI		0.11	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800761; hg19: chr4-100065593;