ENST00000500358.6:n.4160+92G>T

Variant names:

• chr4-99291040-G-T
• rs4147531
• ENST00000500358.6:n.4160+92G>T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.4160+92G>T 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 13 publications found

Genes affected

ENSG00000246090 (HGNC:):

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

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=-0.97).

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.4160+92G>T		intron	N/A
	ADH1A	NM_000667.4	MANE Select	c.-126C>A		upstream_gene	N/A	NP_000658.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.4160+92G>T		intron	N/A
	ENSG00000246090	ENST00000509939.1	TSL:3	n.70+35G>T		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.1268+35G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 800276 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 420204

African (AFR) AF: 0.00 AC: 0 AN: 20232

American (AMR) AF: 0.00 AC: 0 AN: 35804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19438

East Asian (EAS) AF: 0.00 AC: 0 AN: 36588

South Asian (SAS) AF: 0.00 AC: 0 AN: 64136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 532384

Other (OTH) AF: 0.00 AC: 0 AN: 38194

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 26518

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.20
DANN	Benign	0.33
PhyloP100		-1.4
PromoterAI		-0.0076	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4147531; hg19: chr4-100212197;