4-99290629-T-C

Position:

• chr4-99290629-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+268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,010 control chromosomes in the GnomAD database, including 12,731 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 0.39 (12731 hom., cov: 32)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.18+268A>G		intron_variant		ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.4149-308T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.18+268A>G		intron_variant		1	NM_000667.4	ENSP00000209668	P1
	ENST00000500358.6	n.4149-308T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59392 AN: 151890 Hom.: 12729 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.391 AC: 59428 AN: 152010 Hom.: 12731 Cov.: 32 AF XY: 0.387 AC XY: 28780 AN XY: 74282

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.440

Alfa AF: 0.443 Hom.: 18407

Bravo AF: 0.390

Asia WGS AF: 0.227 AC: 790 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.30

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: rs4147532; hg19: chr4-100211786;