chr4-99216337-T-C

Variant names:

• chr4-99216337-T-C
• rs6820368
• NM_001102470.2:c.19-75A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001102470.2(ADH6):​c.19-75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 838,390 control chromosomes in the GnomAD database, including 8 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 0.0046 (1 hom., cov: 28)
  • Exomes 𝑓: 0.00057 (7 hom.)
• Consequence: ADH6 NM_001102470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 4 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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000569 (391/686638) while in subpopulation AFR AF = 0.0185 (286/15474). AF 95% confidence interval is 0.0167. There are 7 homozygotes in GnomAdExome4. There are 165 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	NM_001102470.2	MANE Select	c.19-75A>G		intron	N/A	NP_001095940.1	P28332-2
	ADH6	NM_000672.4		c.19-75A>G		intron	N/A	NP_000663.1	P28332-1
	LOC100507053	NR_037884.1		n.3789+11906T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	ENST00000394899.6	TSL:2 MANE Select	c.19-75A>G		intron	N/A	ENSP00000378359.2	P28332-2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+11906T>C		intron	N/A
	ADH6	ENST00000881183.1		c.19-75A>G		intron	N/A	ENSP00000551242.1

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 692 AN: 151634 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00480

GnomAD4 exome AF: 0.000569 AC: 391 AN: 686638 Hom.: 7 AF XY: 0.000468 AC XY: 165 AN XY: 352358

African (AFR) AF: 0.0185 AC: 286 AN: 15474

American (AMR) AF: 0.00116 AC: 22 AN: 18972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15208

East Asian (EAS) AF: 0.00 AC: 0 AN: 30024

South Asian (SAS) AF: 0.00 AC: 0 AN: 33276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42086

Middle Eastern (MID) AF: 0.00339 AC: 11 AN: 3242

European-Non Finnish (NFE) AF: 0.0000583 AC: 29 AN: 497080

Other (OTH) AF: 0.00137 AC: 43 AN: 31276

GnomAD4 genome AF: 0.00459 AC: 697 AN: 151752 Hom.: 1 Cov.: 28 AF XY: 0.00434 AC XY: 322 AN XY: 74172

African (AFR) AF: 0.0157 AC: 650 AN: 41390

American (AMR) AF: 0.00203 AC: 31 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67924

Other (OTH) AF: 0.00475 AC: 10 AN: 2104

Alfa AF: 0.00275 Hom.: 10

Bravo AF: 0.00517

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6820368; hg19: chr4-100137494;