chr4-99280582-G-C

Variant names:

• chr4-99280582-G-C
• rs975833
• NM_000667.4:c.829-303C>G

Variant summary

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

The NM_000667.4(ADH1A):​c.829-303C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,048 control chromosomes in the GnomAD database, including 6,342 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 0.27 (6342 hom., cov: 32)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH1A	NM_000667.4	c.829-303C>G		intron_variant	Intron 6 of 8	ENST00000209668.3	NP_000658.1
LOC100507053	NR_037884.1	n.3790-6213G>C		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH1A	ENST00000209668.3	c.829-303C>G		intron_variant	Intron 6 of 8	1	NM_000667.4	ENSP00000209668.2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40884 AN: 151930 Hom.: 6349 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.269 AC: 40873 AN: 152048 Hom.: 6342 Cov.: 32 AF XY: 0.270 AC XY: 20082 AN XY: 74332

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.261

Alfa AF: 0.141 Hom.: 231

Bravo AF: 0.270

Asia WGS AF: 0.471 AC: 1635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.72

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: rs975833; hg19: chr4-100201739;