chr4-99088587-G-C

Position:

• chr4-99088587-G-C

Variant summary

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

The ENST00000296412.14(ADH5):​c.12+102C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,286,434 control chromosomes in the GnomAD database, including 304,526 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 0.69 (36020 hom., cov: 31)
  • Exomes 𝑓: 0.68 (268506 hom.)
• Consequence: ADH5 ENST00000296412.14 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH5	NM_000671.4	c.12+102C>G		intron_variant		ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.12+102C>G		intron_variant		1	NM_000671.4	ENSP00000296412	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104030 AN: 151842 Hom.: 35998 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.720

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.674

GnomAD4 exome AF: 0.684 AC: 775549 AN: 1134486 Hom.: 268506 AF XY: 0.686 AC XY: 383747 AN XY: 559192

Gnomad4 AFR exome AF: 0.675

Gnomad4 AMR exome AF: 0.765

Gnomad4 ASJ exome AF: 0.655

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.697

GnomAD4 genome AF: 0.685 AC: 104092 AN: 151948 Hom.: 36020 Cov.: 31 AF XY: 0.694 AC XY: 51521 AN XY: 74236

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.720

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.677

Alfa AF: 0.665 Hom.: 4244

Bravo AF: 0.686

Asia WGS AF: 0.891 AC: 3085 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.5
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1154401; hg19: chr4-100009738;