4-99279352-C-A

Variant names:

• chr4-99279352-C-A
• rs3819197
• NM_000667.4:c.1103+74G>T

Variant summary

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

The NM_000667.4(ADH1A):​c.1103+74G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,472 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: 7.4e-7 (0 hom.)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 19 publications found

Genes affected

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]

ENSG00000246090 (HGNC:):

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=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000667.4. 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
	ADH1A	NM_000667.4	MANE Select	c.1103+74G>T		intron	N/A	NP_000658.1	P07327
	LOC100507053	NR_037884.1		n.3790-7443C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	ENST00000209668.3	TSL:1 MANE Select	c.1103+74G>T		intron	N/A	ENSP00000209668.2	P07327
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-7443C>A		intron	N/A
	ADH1A	ENST00000908169.1		c.1136+74G>T		intron	N/A	ENSP00000578228.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355472 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 668196

African (AFR) AF: 0.00 AC: 0 AN: 28886

American (AMR) AF: 0.00 AC: 0 AN: 27216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20362

East Asian (EAS) AF: 0.00 AC: 0 AN: 37418

South Asian (SAS) AF: 0.0000151 AC: 1 AN: 66380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1065124

Other (OTH) AF: 0.00 AC: 0 AN: 55686

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.44
PhyloP100		-0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3819197; hg19: chr4-100200509;