rs13148577

Variant names:

• chr4-99139685-G-A
• rs13148577
• NM_000670.5:c.263-537C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99139685-G-A
• chr4-99139685-G-C
• chr4-99139685-G-T

Variant summary

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

The NM_000670.5(ADH4):​c.263-537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,916 control chromosomes in the GnomAD database, including 10,416 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 0.34 (10416 hom., cov: 32)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.483 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.263-537C>T		intron	N/A	NP_000661.2	P08319-1
	ADH4	NM_001306171.2		c.320-537C>T		intron	N/A	NP_001293100.1	P08319-2
	ADH4	NM_001306172.2		c.320-537C>T		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.263-537C>T		intron	N/A	ENSP00000265512.7	P08319-1
	ENSG00000246090	ENST00000500358.6	TSL:1	n.679+5880G>A		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.320-537C>T		intron	N/A	ENSP00000425416.1	P08319-2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51622 AN: 151798 Hom.: 10413 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51633 AN: 151916 Hom.: 10416 Cov.: 32 AF XY: 0.343 AC XY: 25475 AN XY: 74238

African (AFR) AF: 0.136 AC: 5616 AN: 41432

American (AMR) AF: 0.331 AC: 5045 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3472

East Asian (EAS) AF: 0.124 AC: 639 AN: 5166

South Asian (SAS) AF: 0.500 AC: 2404 AN: 4812

European-Finnish (FIN) AF: 0.465 AC: 4889 AN: 10508

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30435 AN: 67946

Other (OTH) AF: 0.355 AC: 750 AN: 2110

Alfa AF: 0.393 Hom.: 15680

Bravo AF: 0.315

Asia WGS AF: 0.363 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.49
DANN	Benign	0.67
PhyloP100		-0.86
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: rs13148577; hg19: chr4-100060836;