rs7683802

Variant names:

• chr4-99073987-T-G
• rs7683802
• NM_000671.4:c.961+927A>C

Variant summary

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

The NM_000671.4(ADH5):​c.961+927A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,012 control chromosomes in the GnomAD database, including 643 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 0.089 (643 hom., cov: 32)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4	c.961+927A>C		intron_variant	Intron 7 of 8	ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.961+927A>C		intron_variant	Intron 7 of 8	1	NM_000671.4	ENSP00000296412.8
ADH5	ENST00000626055.2	c.*648+927A>C		intron_variant	Intron 6 of 7	5		ENSP00000487496.1
ADH5	ENST00000512621.5	n.949+927A>C		intron_variant	Intron 6 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13473 AN: 151894 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0347

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0887 AC: 13483 AN: 152012 Hom.: 643 Cov.: 32 AF XY: 0.0835 AC XY: 6208 AN XY: 74316

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.0861

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0349

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0994 Hom.: 1052

Bravo AF: 0.0931

Asia WGS AF: 0.0220 AC: 76 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	0.89
DANN	Benign	0.47

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: rs7683802; hg19: chr4-99995138;