4-99213357-G-T

Position:

• chr4-99213357-G-T

Variant summary

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

The NM_001102470.2(ADH6):​c.262+249C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,816 control chromosomes in the GnomAD database, including 25,365 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 0.57 (25365 hom., cov: 32)
• Consequence: ADH6 NM_001102470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH6	NM_001102470.2	c.262+249C>A		intron_variant		ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4	c.262+249C>A		intron_variant			NP_000663.1
LOC100507053	NR_037884.1	n.3789+8926G>T		intron_variant
ADH6	NR_132990.2	n.214+2804C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899.6	c.262+249C>A		intron_variant		2	NM_001102470.2	ENSP00000378359.2

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86636 AN: 151700 Hom.: 25342 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.571 AC: 86707 AN: 151816 Hom.: 25365 Cov.: 32 AF XY: 0.571 AC XY: 42358 AN XY: 74162

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.573

Alfa AF: 0.525 Hom.: 9026

Bravo AF: 0.585

Asia WGS AF: 0.629 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.55

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: rs4147544; hg19: chr4-100134514;