NM_000669.5:c.567+694G>T

Variant names:

• chr4-99344168-C-A
• rs1625439
• NM_000669.5:c.567+694G>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+694G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,004 control chromosomes in the GnomAD database, including 8,860 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 0.31 (8860 hom., cov: 32)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 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+694G>T		intron	N/A	NP_000660.1
	ADH1C	NR_133005.2		n.638+694G>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+694G>T		intron	N/A	ENSP00000426083.1
	ADH1C	ENST00000865215.1		c.567+694G>T		intron	N/A	ENSP00000535274.1
	ADH1C	ENST00000865216.1		c.567+694G>T		intron	N/A	ENSP00000535275.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47483 AN: 151886 Hom.: 8854 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47503 AN: 152004 Hom.: 8860 Cov.: 32 AF XY: 0.313 AC XY: 23253 AN XY: 74286

African (AFR) AF: 0.144 AC: 5968 AN: 41450

American (AMR) AF: 0.293 AC: 4470 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 941 AN: 3464

East Asian (EAS) AF: 0.0813 AC: 421 AN: 5176

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5422 AN: 10536

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27981 AN: 67972

Other (OTH) AF: 0.282 AC: 593 AN: 2104

Alfa AF: 0.251 Hom.: 803

Bravo AF: 0.287

Asia WGS AF: 0.220 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.27
PhyloP100		-0.38

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: rs1625439; hg19: chr4-100265325;