rs6820368

Positions:

• chr4-99216337-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001102470.2(ADH6):​c.19-75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 838,390 control chromosomes in the GnomAD database, including 8 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 0.0046 (1 hom., cov: 28)
  • Exomes 𝑓: 0.00057 (7 hom.)
• Consequence: ADH6 NM_001102470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000569 (391/686638) while in subpopulation AFR AF= 0.0185 (286/15474). AF 95% confidence interval is 0.0167. There are 7 homozygotes in gnomad4_exome. There are 165 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH6	NM_001102470.2	c.19-75A>G		intron_variant		ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4	c.19-75A>G		intron_variant			NP_000663.1
LOC100507053	NR_037884.1	n.3789+11906T>C		intron_variant
ADH6	NR_132990.2	n.113-75A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899.6	c.19-75A>G		intron_variant		2	NM_001102470.2	ENSP00000378359.2

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 692 AN: 151634 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00480

GnomAD4 exome AF: 0.000569 AC: 391 AN: 686638 Hom.: 7 AF XY: 0.000468 AC XY: 165 AN XY: 352358

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000583

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00459 AC: 697 AN: 151752 Hom.: 1 Cov.: 28 AF XY: 0.00434 AC XY: 322 AN XY: 74172

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00141 Hom.: 2

Bravo AF: 0.00517

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6820368; hg19: chr4-100137494;