rs2000864

Positions:

• chr4-99202619-C-A
• chr4-99202619-C-G
• chr4-99202619-C-T

Variant summary

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

The NR_037884.1(LOC100507053):​n.3715-1738C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 396,300 control chromosomes in the GnomAD database, including 63,587 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 0.56 (24730 hom., cov: 32)
  • Exomes 𝑓: 0.55 (38857 hom.)
• Consequence: LOC100507053 NR_037884.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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
LOC100507053	NR_037884.1	n.3715-1738C>A		intron_variant, non_coding_transcript_variant
ADH6	NM_001102470.2			downstream_gene_variant		ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4			downstream_gene_variant			NP_000663.1
ADH6	NR_132990.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000500358.6	n.3715-1738C>A		intron_variant, non_coding_transcript_variant		1
ADH6	ENST00000394899.6			downstream_gene_variant		2	NM_001102470.2	ENSP00000378359	P1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85451 AN: 151868 Hom.: 24707 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.568

GnomAD4 exome AF: 0.549 AC: 134226 AN: 244316 Hom.: 38857 Cov.: 0 AF XY: 0.549 AC XY: 67969 AN XY: 123882

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.587

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.895

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.563 AC: 85521 AN: 151984 Hom.: 24730 Cov.: 32 AF XY: 0.562 AC XY: 41785 AN XY: 74286

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.566

Alfa AF: 0.516 Hom.: 32423

Bravo AF: 0.578

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	-0.88
CADD	Benign	0.67
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2000864; hg19: chr4-100123776;