4-99203559-C-G

Position:

• chr4-99203559-C-G

Variant summary

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

The NM_001102470.2(ADH6):​c.*660G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,916 control chromosomes in the GnomAD database, including 32,060 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 (32057 hom., cov: 31)
  • Exomes 𝑓: 0.55 (3 hom.)
• Consequence: ADH6 NM_001102470.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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 = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH6	NM_001102470.2	c.*660G>C		3_prime_UTR_variant	9/9	ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4	c.*1362G>C		3_prime_UTR_variant	8/8		NP_000663.1
ADH6	NR_132990.2	n.1523G>C		non_coding_transcript_exon_variant	7/7
LOC100507053	NR_037884.1	n.3715-798C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899	c.*660G>C		3_prime_UTR_variant	9/9	2	NM_001102470.2	ENSP00000378359.2

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96197 AN: 151776 Hom.: 32005 Cov.: 31

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.550 AC: 11 AN: 20 Hom.: 3 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.634 AC: 96304 AN: 151896 Hom.: 32057 Cov.: 31 AF XY: 0.632 AC XY: 46917 AN XY: 74206

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.617

Alfa AF: 0.568 Hom.: 2997

Bravo AF: 0.654

Asia WGS AF: 0.646 AC: 2246 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	1.2
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1893883; hg19: chr4-100124716;