rs11936869

Positions:

• chr4-99352016-C-G
• chr4-99352016-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.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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH1C	NM_000669.5	c.18+642G>C		intron_variant		ENST00000515683.6
ADH1C	NR_133005.2	n.89+642G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH1C	ENST00000515683.6	c.18+642G>C		intron_variant		1	NM_000669.5	P1
ADH1C	ENST00000510055.5	c.-223+642G>C		intron_variant		3
ADH1C	ENST00000511397.3	c.18+642G>C		intron_variant		3
ADH1C	ENST00000505942.2	n.87+642G>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.754

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.308

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 v4.3

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

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: rs11936869; hg19: chr4-100273173;