rs4699699

Positions:

• chr4-99076028-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000671.4(ADH5):​c.825+264G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 406,130 control chromosomes in the GnomAD database, including 1,594 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 0.084 (577 hom., cov: 32)
  • Exomes 𝑓: 0.080 (1017 hom.)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833

Genes affected

ADH5 (HGNC:253): (alcohol dehydrogenase 5 (class III), chi polypeptide) This gene encodes a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein forms a homodimer. It has virtually no activity for ethanol oxidation, but exhibits high activity for oxidation of long-chain primary alcohols and for oxidation of S-hydroxymethyl-glutathione, a spontaneous adduct between formaldehyde and glutathione. This enzyme is an important component of cellular metabolism for the elimination of formaldehyde, a potent irritant and sensitizing agent that causes lacrymation, rhinitis, pharyngitis, and contact dermatitis. The human genome contains several non-transcribed pseudogenes related to this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADH5	NM_000671.4	c.825+264G>C		intron_variant		ENST00000296412.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADH5	ENST00000296412.14	c.825+264G>C		intron_variant		1	NM_000671.4	P1

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12795 AN: 152128 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0992

GnomAD4 exome AF: 0.0800 AC: 20304 AN: 253884 Hom.: 1017 Cov.: 3 AF XY: 0.0762 AC XY: 10252 AN XY: 134498

Gnomad4 AFR exome AF: 0.0800

Gnomad4 AMR exome AF: 0.0716

Gnomad4 ASJ exome AF: 0.0896

Gnomad4 EAS exome AF: 0.000207

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0507

Gnomad4 NFE exome AF: 0.0988

Gnomad4 OTH exome AF: 0.0874

GnomAD4 genome AF: 0.0841 AC: 12803 AN: 152246 Hom.: 577 Cov.: 32 AF XY: 0.0792 AC XY: 5897 AN XY: 74442

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.0856

Gnomad4 ASJ AF: 0.0861

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0982

Alfa AF: 0.0891 Hom.: 78

Bravo AF: 0.0880

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.57
DANN	Benign	0.43

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: rs4699699; hg19: chr4-99997179;