rs931635

Positions:

• chr4-99289690-A-G

Variant summary

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

The NM_000667.4(ADH1A):​c.18+1207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,136 control chromosomes in the GnomAD database, including 51,177 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 0.82 (51177 hom., cov: 33)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

Genes affected

ADH1A (HGNC:249): (alcohol dehydrogenase 1A (class I), alpha polypeptide) This gene encodes a member of the alcohol dehydrogenase family. The encoded protein is the alpha subunit of class I alcohol dehydrogenase, which consists of several homo- and heterodimers of alpha, beta and gamma subunits. Alcohol dehydrogenases catalyze the oxidation of alcohols to aldehydes. This gene is active in the liver in early fetal life but only weakly active in adult liver. This gene is found in a cluster with six additional alcohol dehydrogenase genes, including those encoding the beta and gamma subunits, on the long arm of chromosome 4. Mutations in this gene may contribute to variation in certain personality traits and substance dependence. [provided by RefSeq, Nov 2010]

ENSG00000246090 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.18+1207T>C		intron_variant		ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.4148+905A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.18+1207T>C		intron_variant		1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124266 AN: 152018 Hom.: 51124 Cov.: 33

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.818 AC: 124374 AN: 152136 Hom.: 51177 Cov.: 33 AF XY: 0.813 AC XY: 60425 AN XY: 74362

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.824

Alfa AF: 0.792 Hom.: 19183

Bravo AF: 0.832

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.52

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: rs931635; hg19: chr4-100210847;