chr4-99208528-C-T

Position:

• chr4-99208528-C-T

Variant summary

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

The NM_001102470.2(ADH6):​c.828+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 919,136 control chromosomes in the GnomAD database, including 73,068 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 0.42 (14934 hom., cov: 32)
  • Exomes 𝑓: 0.36 (58134 hom.)
• Consequence: ADH6 NM_001102470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH6	NM_001102470.2	c.828+140G>A		intron_variant		ENST00000394899.6	NP_001095940.1
ADH6	NM_000672.4	c.828+140G>A		intron_variant			NP_000663.1
LOC100507053	NR_037884.1	n.3789+4097C>T		intron_variant
ADH6	NR_132990.2	n.563+140G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH6	ENST00000394899.6	c.828+140G>A		intron_variant		2	NM_001102470.2	ENSP00000378359.2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64037 AN: 151748 Hom.: 14918 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.364 AC: 279555 AN: 767270 Hom.: 58134 Cov.: 10 AF XY: 0.367 AC XY: 143636 AN XY: 391236

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.891

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.422 AC: 64094 AN: 151866 Hom.: 14934 Cov.: 32 AF XY: 0.425 AC XY: 31539 AN XY: 74228

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.403

Alfa AF: 0.352 Hom.: 20355

Bravo AF: 0.443

Asia WGS AF: 0.579 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.68

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: rs3857224; hg19: chr4-100129685;