rs13112924

Positions:

• chr4-99129258-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000670.5(ADH4):​c.844-1914T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 152,198 control chromosomes in the GnomAD database, including 12 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 0.011 (12 hom., cov: 33)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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=-0.69).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0109 (1666/152198) while in subpopulation NFE AF= 0.0173 (1179/67986). AF 95% confidence interval is 0.0165. There are 12 homozygotes in gnomad4. There are 757 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH4	NM_000670.5	c.844-1914T>C		intron_variant		ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.901-1914T>C		intron_variant			NP_001293100.1
ADH4	NM_001306172.2	c.901-1914T>C		intron_variant			NP_001293101.1
LOC100507053	NR_037884.1	n.429-4297A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.844-1914T>C		intron_variant		1	NM_000670.5	ENSP00000265512.7

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1666 AN: 152080 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00304

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.000948

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0109 AC: 1666 AN: 152198 Hom.: 12 Cov.: 33 AF XY: 0.0102 AC XY: 757 AN XY: 74436

Gnomad4 AFR AF: 0.00303

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.000948

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0139 Hom.: 2

Bravo AF: 0.0117

Asia WGS AF: 0.00291 AC: 10 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.95

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: rs13112924; hg19: chr4-100050409;