rs4147545

Positions:

• chr4-99207596-T-C

Variant summary

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

The NM_001102470.2(ADH6):​c.829-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,610,410 control chromosomes in the GnomAD database, including 120,390 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 0.43 (15308 hom., cov: 32)
  • Exomes 𝑓: 0.36 (105082 hom.)
• Consequence: ADH6 NM_001102470.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH6	NM_001102470.2	c.829-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000394899.6
LOC100507053	NR_037884.1	n.3789+3165T>C		intron_variant, non_coding_transcript_variant
ADH6	NM_000672.4	c.829-15A>G		splice_polypyrimidine_tract_variant, intron_variant
ADH6	NR_132990.2	n.564-15A>G		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH6	ENST00000394899.6	c.829-15A>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_001102470.2	P1
	ENST00000500358.6	n.3789+3165T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65154 AN: 151828 Hom.: 15295 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.411

GnomAD3 exomes AF: 0.427 AC: 106112 AN: 248636 Hom.: 25524 AF XY: 0.419 AC XY: 56217 AN XY: 134320

Gnomad AFR exome AF: 0.566

Gnomad AMR exome AF: 0.503

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.886

Gnomad SAS exome AF: 0.436

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.378

GnomAD4 exome AF: 0.363 AC: 529539 AN: 1458464 Hom.: 105082 Cov.: 34 AF XY: 0.365 AC XY: 264947 AN XY: 725524

Gnomad4 AFR exome AF: 0.568

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.890

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.429 AC: 65209 AN: 151946 Hom.: 15308 Cov.: 32 AF XY: 0.432 AC XY: 32086 AN XY: 74276

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.410

Alfa AF: 0.362 Hom.: 14025

Bravo AF: 0.450

Asia WGS AF: 0.580 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4147545; hg19: chr4-100128753;