4-99208528-C-T

Variant names:

• chr4-99208528-C-T
• rs3857224
• NM_001102470.2:c.828+140G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102470.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	NM_001102470.2	MANE Select	c.828+140G>A		intron	N/A	NP_001095940.1
	ADH6	NM_000672.4		c.828+140G>A		intron	N/A	NP_000663.1
	LOC100507053	NR_037884.1		n.3789+4097C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	ENST00000394899.6	TSL:2 MANE Select	c.828+140G>A		intron	N/A	ENSP00000378359.2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+4097C>T		intron	N/A
	ADH6	ENST00000504257.1	TSL:3	n.611G>A		non_coding_transcript_exon	Exon 2 of 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

African (AFR) AF: 0.564 AC: 10335 AN: 18320

American (AMR) AF: 0.477 AC: 10339 AN: 21672

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 5311 AN: 15730

East Asian (EAS) AF: 0.891 AC: 31051 AN: 34860

South Asian (SAS) AF: 0.443 AC: 22254 AN: 50248

European-Finnish (FIN) AF: 0.286 AC: 12465 AN: 43514

Middle Eastern (MID) AF: 0.351 AC: 968 AN: 2760

European-Non Finnish (NFE) AF: 0.319 AC: 173334 AN: 543772

Other (OTH) AF: 0.371 AC: 13498 AN: 36394

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

African (AFR) AF: 0.558 AC: 23127 AN: 41414

American (AMR) AF: 0.458 AC: 6977 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3468

East Asian (EAS) AF: 0.877 AC: 4541 AN: 5178

South Asian (SAS) AF: 0.480 AC: 2312 AN: 4820

European-Finnish (FIN) AF: 0.284 AC: 2985 AN: 10522

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21717 AN: 67930

Other (OTH) AF: 0.403 AC: 848 AN: 2102

Alfa AF: 0.366 Hom.: 34069

Bravo AF: 0.443

Asia WGS AF: 0.579 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.68
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3857224; hg19: chr4-100129685;