rs4147531

Positions:

• chr4-99291040-G-A
• chr4-99291040-G-T

Variant summary

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

The NR_037884.1(LOC100507053):​n.4160+92G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 949,306 control chromosomes in the GnomAD database, including 88,908 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 0.39 (12645 hom., cov: 31)
  • Exomes 𝑓: 0.42 (76263 hom.)
• Consequence: LOC100507053 NR_037884.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

(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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC100507053	NR_037884.1	n.4160+92G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000500358.6	n.4160+92G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59174 AN: 151532 Hom.: 12643 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.419 AC: 334225 AN: 797656 Hom.: 76263 Cov.: 10 AF XY: 0.412 AC XY: 172722 AN XY: 418848

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.0956

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.390 AC: 59210 AN: 151650 Hom.: 12645 Cov.: 31 AF XY: 0.387 AC XY: 28647 AN XY: 74102

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.439

Alfa AF: 0.456 Hom.: 21181

Bravo AF: 0.390

Asia WGS AF: 0.226 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4147531; hg19: chr4-100212197; COSMIC: COSV52925045;