4-99207596-T-C

Variant names:

• chr4-99207596-T-C
• rs4147545
• NM_001102470.2:c.829-15A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102470.2(ADH6):​c.829-15A>G variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 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.829-15A>G		intron	N/A	NP_001095940.1
	ADH6	NM_000672.4		c.829-15A>G		intron	N/A	NP_000663.1
	LOC100507053	NR_037884.1		n.3789+3165T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	ENST00000394899.6	TSL:2 MANE Select	c.829-15A>G		intron	N/A	ENSP00000378359.2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+3165T>C		intron	N/A
	ENSG00000246090	ENST00000757805.1		n.1014T>C		non_coding_transcript_exon	Exon 5 of 5

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

GnomAD2 exomes AF: 0.427 AC: 106112 AN: 248636 AF XY: 0.419

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 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

African (AFR) AF: 0.568 AC: 18963 AN: 33370

American (AMR) AF: 0.497 AC: 22044 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8827 AN: 26056

East Asian (EAS) AF: 0.890 AC: 35283 AN: 39648

South Asian (SAS) AF: 0.443 AC: 38189 AN: 86122

European-Finnish (FIN) AF: 0.297 AC: 15816 AN: 53320

Middle Eastern (MID) AF: 0.347 AC: 1996 AN: 5754

European-Non Finnish (NFE) AF: 0.330 AC: 365639 AN: 1109592

Other (OTH) AF: 0.378 AC: 22782 AN: 60236

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

African (AFR) AF: 0.559 AC: 23175 AN: 41438

American (AMR) AF: 0.465 AC: 7093 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3466

East Asian (EAS) AF: 0.877 AC: 4515 AN: 5150

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4820

European-Finnish (FIN) AF: 0.298 AC: 3152 AN: 10564

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22495 AN: 67940

Other (OTH) AF: 0.410 AC: 864 AN: 2108

Alfa AF: 0.369 Hom.: 18404

Bravo AF: 0.450

Asia WGS AF: 0.580 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.67
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4147545; hg19: chr4-100128753;