4-99125534-T-C

Variant names:

• chr4-99125534-T-C
• rs1573495
• NM_000670.5:c.1118+1060A>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.1118+1060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,326 control chromosomes in the GnomAD database, including 70,057 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 0.96 (70057 hom., cov: 33)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	NM_000670.5	MANE Select	c.1118+1060A>G		intron	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.1175+1060A>G		intron	N/A	NP_001293100.1
	ADH4	NM_001306172.2		c.1175+1060A>G		intron	N/A	NP_001293101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.1118+1060A>G		intron	N/A	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.429-8021T>C		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.1175+1060A>G		intron	N/A	ENSP00000425416.1

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145959 AN: 152208 Hom.: 70007 Cov.: 33

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.959 AC: 146068 AN: 152326 Hom.: 70057 Cov.: 33 AF XY: 0.959 AC XY: 71456 AN XY: 74492

African (AFR) AF: 0.934 AC: 38794 AN: 41546

American (AMR) AF: 0.956 AC: 14644 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3378 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5186

South Asian (SAS) AF: 0.979 AC: 4722 AN: 4824

European-Finnish (FIN) AF: 0.944 AC: 10031 AN: 10622

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66085 AN: 68044

Other (OTH) AF: 0.968 AC: 2047 AN: 2114

Alfa AF: 0.965 Hom.: 36612

Bravo AF: 0.957

Asia WGS AF: 0.977 AC: 3399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.45
PhyloP100		-0.71
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: rs1573495; hg19: chr4-100046685;