rs283411

chr4-99344800-C-Achr4-99344800-C-T

Variant summary

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

The NM_000669.5(ADH1C):c.567+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,588,928 control chromosomes in the GnomAD database, including 3,490 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 0.066 (368 hom., cov: 33)
  • Exomes 𝑓: 0.063 (3122 hom.)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

Genes affected

ADH1C (HGNC:251): (alcohol dehydrogenase 1C (class I), gamma polypeptide) This gene encodes class I alcohol dehydrogenase, gamma 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 I alcohol dehydrogenase, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation to acetaldehyde, thus playing a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. An association between ADH1C polymorphism and alcohol dependence has not been established. [provided by RefSeq, Sep 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1C	NM_000669.5	c.567+62G>T		intron_variant		ENST00000515683.6
ADH1C	NR_133005.2	n.638+62G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1C	ENST00000515683.6	c.567+62G>T		intron_variant		1	NM_000669.5	P1
ADH1C	ENST00000510055.5	c.447+62G>T		intron_variant		3
ADH1C	ENST00000511397.3	c.465+62G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10027 AN: 152122 Hom.: 366 Cov.: 33

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0747

GnomAD4 exome AF: 0.0631 AC: 90596 AN: 1436688 Hom.: 3122 AF XY: 0.0623 AC XY: 44452 AN XY: 713692

Gnomad4 AFR exome AF: 0.0583

Gnomad4 AMR exome AF: 0.0419

Gnomad4 ASJ exome AF: 0.0993

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0237

Gnomad4 FIN exome AF: 0.0944

Gnomad4 NFE exome AF: 0.0669

Gnomad4 OTH exome AF: 0.0634

GnomAD4 genome AF: 0.0659 AC: 10039 AN: 152240 Hom.: 368 Cov.: 33 AF XY: 0.0644 AC XY: 4795 AN XY: 74434

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0190

Gnomad4 FIN AF: 0.0994

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0222 Hom.: 12

Bravo AF: 0.0657

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.2
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs283411; hg19: chr4-100265957; COSMIC: COSV72463449; COSMIC: COSV72463449;