rs4148886

chr4-99143498-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.18+707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 285,438 control chromosomes in the GnomAD database, including 22,087 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 0.36 (12034 hom., cov: 32)
  • Exomes 𝑓: 0.34 (10053 hom.)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH4	NM_000670.5	c.18+707A>G		intron_variant		ENST00000265512.12
LOC100507053	NR_037884.1	n.679+9693T>C		intron_variant, non_coding_transcript_variant
ADH4	NM_001306171.2	c.-65-193A>G		intron_variant
ADH4	NM_001306172.2	c.-65-193A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH4	ENST00000265512.12	c.18+707A>G		intron_variant		1	NM_000670.5	P1
	ENST00000500358.6	n.679+9693T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55102 AN: 151840 Hom.: 12016 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.338 AC: 45162 AN: 133480 Hom.: 10053 AF XY: 0.340 AC XY: 23850 AN XY: 70250

Gnomad4 AFR exome AF: 0.564

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.900

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.363 AC: 55168 AN: 151958 Hom.: 12034 Cov.: 32 AF XY: 0.368 AC XY: 27335 AN XY: 74266

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.334

Alfa AF: 0.279 Hom.: 1372

Bravo AF: 0.387

Asia WGS AF: 0.529 AC: 1818 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.9
Dann	Benign	0.87

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: rs4148886; hg19: chr4-100064649;