rs6833176

Positions:

• chr4-99210006-G-C
• chr4-99210006-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.567+76C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,440,230 control chromosomes in the GnomAD database, including 231,794 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 0.63 (32083 hom., cov: 32)
  • Exomes 𝑓: 0.55 (199711 hom.)
• Consequence: ADH6 NM_001102470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH6	NM_001102470.2	c.567+76C>G		intron_variant		ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4	c.567+76C>G		intron_variant			NP_000663.1
LOC100507053	NR_037884.1	n.3789+5575G>C		intron_variant
ADH6	NR_132990.2	n.302+409C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899.6	c.567+76C>G		intron_variant		2	NM_001102470.2	ENSP00000378359.2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96273 AN: 151892 Hom.: 32031 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.549 AC: 707872 AN: 1288220 Hom.: 199711 AF XY: 0.549 AC XY: 355471 AN XY: 647340

Gnomad4 AFR exome AF: 0.841

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.891

Gnomad4 SAS exome AF: 0.552

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.561

GnomAD4 genome AF: 0.634 AC: 96380 AN: 152010 Hom.: 32083 Cov.: 32 AF XY: 0.632 AC XY: 46985 AN XY: 74294

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.617

Alfa AF: 0.410 Hom.: 975

Bravo AF: 0.654

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.28
DANN	Benign	0.73

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: rs6833176; hg19: chr4-100131163; COSMIC: COSV52956624; COSMIC: COSV52956624;