NM_000670.5:c.18+707A>G

Variant names:

• chr4-99143498-T-C
• rs4148886
• NM_000670.5:c.18+707A>G

Variant summary

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

The NM_000670.5(ADH4):​c.18+707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 285,438 control chromosomes in the GnomAD database, including 22,087 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 0.36 (12034 hom., cov: 32)
  • Exomes 𝑓: 0.34 (10053 hom.)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 7 publications found

Genes affected

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [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 = 0.853 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. 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
	ADH4	NM_000670.5	MANE Select	c.18+707A>G		intron	N/A	NP_000661.2	P08319-1
	ADH4	NM_001306171.2		c.-65-193A>G		intron	N/A	NP_001293100.1	P08319-2
	ADH4	NM_001306172.2		c.-65-193A>G		intron	N/A	NP_001293101.1	P08319-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.18+707A>G		intron	N/A	ENSP00000265512.7	P08319-1
	ENSG00000246090	ENST00000500358.6	TSL:1	n.679+9693T>C		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.-65-193A>G		intron	N/A	ENSP00000425416.1	P08319-2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55102 AN: 151840 Hom.: 12016 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.338 AC: 45162 AN: 133480 Hom.: 10053 AF XY: 0.340 AC XY: 23850 AN XY: 70250

African (AFR) AF: 0.564 AC: 2720 AN: 4824

American (AMR) AF: 0.433 AC: 2811 AN: 6498

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1232 AN: 4280

East Asian (EAS) AF: 0.900 AC: 9714 AN: 10788

South Asian (SAS) AF: 0.370 AC: 3712 AN: 10036

European-Finnish (FIN) AF: 0.250 AC: 1457 AN: 5820

Middle Eastern (MID) AF: 0.337 AC: 186 AN: 552

European-Non Finnish (NFE) AF: 0.250 AC: 20730 AN: 82790

Other (OTH) AF: 0.329 AC: 2600 AN: 7892

GnomAD4 genome AF: 0.363 AC: 55168 AN: 151958 Hom.: 12034 Cov.: 32 AF XY: 0.368 AC XY: 27335 AN XY: 74266

African (AFR) AF: 0.535 AC: 22158 AN: 41442

American (AMR) AF: 0.399 AC: 6087 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3466

East Asian (EAS) AF: 0.875 AC: 4527 AN: 5176

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4818

European-Finnish (FIN) AF: 0.246 AC: 2589 AN: 10536

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16094 AN: 67946

Other (OTH) AF: 0.334 AC: 704 AN: 2106

Alfa AF: 0.279 Hom.: 1372

Bravo AF: 0.387

Asia WGS AF: 0.529 AC: 1818 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.87
PhyloP100		0.25
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: rs4148886; hg19: chr4-100064649;