4-99213635-A-G

Variant names:

• chr4-99213635-A-G
• rs150883702
• NM_001102470.2:c.233T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001102470.2(ADH6):​c.233T>C​(p.Ile78Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: ADH6 NM_001102470.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.10
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07467109).

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.233T>C	p.Ile78Thr	missense	Exon 3 of 9	NP_001095940.1	P28332-2
	ADH6	NM_000672.4		c.233T>C	p.Ile78Thr	missense	Exon 3 of 8	NP_000663.1	P28332-1
	LOC100507053	NR_037884.1		n.3789+9204A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH6	ENST00000394899.6	TSL:2 MANE Select	c.233T>C	p.Ile78Thr	missense	Exon 3 of 9	ENSP00000378359.2	P28332-2
	ENSG00000246090	ENST00000500358.6	TSL:1	n.3789+9204A>G		intron	N/A
	ADH6	ENST00000881183.1		c.254T>C	p.Ile85Thr	missense	Exon 3 of 9	ENSP00000551242.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000439 AC: 110 AN: 250562 AF XY: 0.000414

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.000697

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000355 AC: 518 AN: 1461208 Hom.: 0 Cov.: 31 AF XY: 0.000347 AC XY: 252 AN XY: 726930

African (AFR) AF: 0.0000897 AC: 3 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00152 AC: 81 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000373 AC: 415 AN: 1111760

Other (OTH) AF: 0.000315 AC: 19 AN: 60358

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74368

African (AFR) AF: 0.000120 AC: 5 AN: 41506

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000629 Hom.: 0

Bravo AF: 0.000151

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000502 AC: 61

EpiCase AF: 0.000164

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.65
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.47	N
PhyloP100		8.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.027	D
Polyphen		0.019	B
Vest4		0.46
MVP		0.25
MPC		0.14
ClinPred		0.10	T
GERP RS		3.6
Varity_R		0.062
gMVP		0.53
Mutation Taster		=91/9	polymorphism

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: rs150883702; hg19: chr4-100134792;