chr4-99344800-C-A

Variant names:

• chr4-99344800-C-A
• rs283411
• NM_000669.5:c.567+62G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000669.5. 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
	ADH1C	NM_000669.5	MANE Select	c.567+62G>T		intron	N/A	NP_000660.1
	ADH1C	NR_133005.2		n.638+62G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1C	ENST00000515683.6	TSL:1 MANE Select	c.567+62G>T		intron	N/A	ENSP00000426083.1
	ADH1C	ENST00000510055.5	TSL:3	c.447+62G>T		intron	N/A	ENSP00000478439.1
	ADH1C	ENST00000511397.3	TSL:3	c.465+62G>T		intron	N/A	ENSP00000478545.1

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

African (AFR) AF: 0.0583 AC: 1903 AN: 32618

American (AMR) AF: 0.0419 AC: 1769 AN: 42250

Ashkenazi Jewish (ASJ) AF: 0.0993 AC: 2547 AN: 25640

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39428

South Asian (SAS) AF: 0.0237 AC: 2000 AN: 84556

European-Finnish (FIN) AF: 0.0944 AC: 5016 AN: 53140

Middle Eastern (MID) AF: 0.0735 AC: 416 AN: 5662

European-Non Finnish (NFE) AF: 0.0669 AC: 73178 AN: 1094030

Other (OTH) AF: 0.0634 AC: 3763 AN: 59364

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

African (AFR) AF: 0.0610 AC: 2533 AN: 41542

American (AMR) AF: 0.0628 AC: 961 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0190 AC: 92 AN: 4830

European-Finnish (FIN) AF: 0.0994 AC: 1052 AN: 10586

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4709 AN: 68014

Other (OTH) AF: 0.0735 AC: 155 AN: 2110

Alfa AF: 0.0572 Hom.: 440

Bravo AF: 0.0657

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.72
PhyloP100		-0.65

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

Other links and lift over

dbSNP: rs283411; hg19: chr4-100265957; COSMIC: COSV72463449; COSMIC: COSV72463449;