chr4-99125534-T-C

Position:

• chr4-99125534-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH4	NM_000670.5	c.1118+1060A>G		intron_variant		ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.1175+1060A>G		intron_variant			NP_001293100.1
ADH4	NM_001306172.2	c.1175+1060A>G		intron_variant			NP_001293101.1
LOC100507053	NR_037884.1	n.429-8021T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.1118+1060A>G		intron_variant		1	NM_000670.5	ENSP00000265512.7

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

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.956

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.979

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.968

Alfa AF: 0.963 Hom.: 20083

Bravo AF: 0.957

Asia WGS AF: 0.977 AC: 3399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1573495; hg19: chr4-100046685;