rs11936869

Variant names:

• chr4-99352016-C-G
• rs11936869
• NM_000669.5:c.18+642G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-99352016-C-G
• chr4-99352016-C-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.18+642G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,996 control chromosomes in the GnomAD database, including 9,958 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 0.34 (9958 hom., cov: 33)
• Consequence: ADH1C NM_000669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 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.18+642G>C		intron	N/A	NP_000660.1
	ADH1C	NR_133005.2		n.89+642G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1C	ENST00000515683.6	TSL:1 MANE Select	c.18+642G>C		intron	N/A	ENSP00000426083.1
	ADH1C	ENST00000510055.5	TSL:3	c.-223+642G>C		intron	N/A	ENSP00000478439.1
	ADH1C	ENST00000511397.3	TSL:3	c.18+642G>C		intron	N/A	ENSP00000478545.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51058 AN: 151878 Hom.: 9958 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.336 AC: 51086 AN: 151996 Hom.: 9958 Cov.: 33 AF XY: 0.340 AC XY: 25244 AN XY: 74256

African (AFR) AF: 0.468 AC: 19392 AN: 41462

American (AMR) AF: 0.222 AC: 3392 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3466

East Asian (EAS) AF: 0.754 AC: 3905 AN: 5176

South Asian (SAS) AF: 0.548 AC: 2637 AN: 4812

European-Finnish (FIN) AF: 0.191 AC: 2009 AN: 10538

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18014 AN: 67956

Other (OTH) AF: 0.308 AC: 650 AN: 2108

Alfa AF: 0.279 Hom.: 832

Bravo AF: 0.337

Asia WGS AF: 0.515 AC: 1790 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		0.17

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: rs11936869; hg19: chr4-100273173;