rs3805325

Positions:

• chr4-99290242-T-C

Variant summary

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

The NM_000667.4(ADH1A):​c.18+655A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,180 control chromosomes in the GnomAD database, including 1,317 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 0.11 (1317 hom., cov: 33)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.18+655A>G		intron_variant		ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.4149-695T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.18+655A>G		intron_variant		1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17424 AN: 152062 Hom.: 1311 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.0593

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.115 AC: 17457 AN: 152180 Hom.: 1317 Cov.: 33 AF XY: 0.118 AC XY: 8757 AN XY: 74396

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.0828

Gnomad4 EAS AF: 0.0892

Gnomad4 SAS AF: 0.0602

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.110

Alfa AF: 0.103 Hom.: 118

Bravo AF: 0.128

Asia WGS AF: 0.129 AC: 446 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.79

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: rs3805325; hg19: chr4-100211399;