rs1229970

Variant names:

• chr4-99283223-A-C
• rs1229970
• NM_000667.4:c.568-617T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99283223-A-C
• chr4-99283223-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000667.4(ADH1A):​c.568-617T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,120 control chromosomes in the GnomAD database, including 51,022 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 (51022 hom., cov: 31)
• Consequence: ADH1A NM_000667.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000667.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	NM_000667.4	MANE Select	c.568-617T>G		intron	N/A	NP_000658.1	P07327
	LOC100507053	NR_037884.1		n.3790-3572A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1A	ENST00000209668.3	TSL:1 MANE Select	c.568-617T>G		intron	N/A	ENSP00000209668.2	P07327
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3790-3572A>C		intron	N/A
	ADH1A	ENST00000503461.5	TSL:1	n.610-617T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124070 AN: 152004 Hom.: 50969 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.805

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: 0.774

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.816 AC: 124178 AN: 152120 Hom.: 51022 Cov.: 31 AF XY: 0.811 AC XY: 60319 AN XY: 74332

African (AFR) AF: 0.910 AC: 37774 AN: 41516

American (AMR) AF: 0.805 AC: 12301 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4713 AN: 5172

South Asian (SAS) AF: 0.701 AC: 3374 AN: 4816

European-Finnish (FIN) AF: 0.734 AC: 7740 AN: 10548

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52649 AN: 68002

Other (OTH) AF: 0.821 AC: 1733 AN: 2110

Alfa AF: 0.795 Hom.: 5995

Bravo AF: 0.830

Asia WGS AF: 0.748 AC: 2594 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.69
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1229970; hg19: chr4-100204380;