4-99279352-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000667.4(ADH1A):​c.1103+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,506,158 control chromosomes in the GnomAD database, including 60,893 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 0.27 (6344 hom., cov: 32)
  • Exomes 𝑓: 0.26 (54549 hom.)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.1103+74G>A		intron_variant	Intron 8 of 8	ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.3790-7443C>T		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.1103+74G>A		intron_variant	Intron 8 of 8	1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40852 AN: 151856 Hom.: 6350 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.261 AC: 353290 AN: 1354184 Hom.: 54549 AF XY: 0.266 AC XY: 177405 AN XY: 667532

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.240

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.269 AC: 40842 AN: 151974 Hom.: 6344 Cov.: 32 AF XY: 0.270 AC XY: 20064 AN XY: 74266

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.260

Alfa AF: 0.259 Hom.: 6763

Bravo AF: 0.270

Asia WGS AF: 0.470 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3819197; hg19: chr4-100200509; COSMIC: COSV52925066; COSMIC: COSV52925066;