rs13148577

chr4-99139685-G-Achr4-99139685-G-Cchr4-99139685-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH4	NM_000670.5	c.263-537C>T		intron_variant		ENST00000265512.12
LOC100507053	NR_037884.1	n.679+5880G>A		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2	c.320-537C>T		intron_variant
ADH4	NM_001306172.2	c.320-537C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH4	ENST00000265512.12	c.263-537C>T		intron_variant		1	NM_000670.5	P1
	ENST00000500358.6	n.679+5880G>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.355

Alfa AF: 0.404 Hom.: 12309

Bravo AF: 0.315

Asia WGS AF: 0.363 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.49
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs13148577; hg19: chr4-100060836;