4-99216377-G-C

Variant names:

• chr4-99216377-G-C
• rs4699733
• NM_001102470.2:c.19-115C>G

Variant summary

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

The NM_001102470.2(ADH6):​c.19-115C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 470,636 control chromosomes in the GnomAD database, including 118,301 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 0.69 (36439 hom., cov: 27)
  • Exomes 𝑓: 0.71 (81862 hom.)
• Consequence: ADH6 NM_001102470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734
• Publications: 7 publications found

Genes affected

ADH6 (HGNC:255): (alcohol dehydrogenase 6 (class V)) This gene encodes class V alcohol dehydrogenase, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This gene is expressed in the stomach as well as in the liver, and it contains a glucocorticoid response element upstream of its 5' UTR, which is a steroid hormone receptor binding site. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000246090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102470.2. 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
	ADH6	NM_001102470.2	MANE Select	c.19-115C>G		intron	N/A	NP_001095940.1	P28332-2
	ADH6	NM_000672.4		c.19-115C>G		intron	N/A	NP_000663.1	P28332-1
	LOC100507053	NR_037884.1		n.3789+11946G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	ENST00000394899.6	TSL:2 MANE Select	c.19-115C>G		intron	N/A	ENSP00000378359.2	P28332-2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+11946G>C		intron	N/A
	ADH6	ENST00000881183.1		c.19-115C>G		intron	N/A	ENSP00000551242.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 104481 AN: 150630 Hom.: 36420 Cov.: 27

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.708 AC: 226557 AN: 319892 Hom.: 81862 AF XY: 0.709 AC XY: 117004 AN XY: 164938

African (AFR) AF: 0.658 AC: 5636 AN: 8560

American (AMR) AF: 0.691 AC: 6215 AN: 8998

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 7861 AN: 9816

East Asian (EAS) AF: 0.911 AC: 21709 AN: 23820

South Asian (SAS) AF: 0.634 AC: 5308 AN: 8370

European-Finnish (FIN) AF: 0.624 AC: 17574 AN: 28142

Middle Eastern (MID) AF: 0.718 AC: 1098 AN: 1530

European-Non Finnish (NFE) AF: 0.698 AC: 148272 AN: 212516

Other (OTH) AF: 0.710 AC: 12884 AN: 18140

GnomAD4 genome AF: 0.694 AC: 104544 AN: 150744 Hom.: 36439 Cov.: 27 AF XY: 0.691 AC XY: 50782 AN XY: 73524

African (AFR) AF: 0.651 AC: 26773 AN: 41098

American (AMR) AF: 0.722 AC: 10935 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2764 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4664 AN: 5150

South Asian (SAS) AF: 0.669 AC: 3196 AN: 4776

European-Finnish (FIN) AF: 0.624 AC: 6306 AN: 10106

Middle Eastern (MID) AF: 0.731 AC: 212 AN: 290

European-Non Finnish (NFE) AF: 0.701 AC: 47460 AN: 67688

Other (OTH) AF: 0.724 AC: 1525 AN: 2106

Alfa AF: 0.577 Hom.: 1581

Bravo AF: 0.699

Asia WGS AF: 0.692 AC: 2402 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.30
PhyloP100		-0.73
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: rs4699733; hg19: chr4-100137534;