4-99080096-T-C

Variant names:

• chr4-99080096-T-C
• rs1154412
• NM_000671.4:c.344+1269A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000671.4(ADH5):​c.344+1269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 386,808 control chromosomes in the GnomAD database, including 139,831 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 0.86 (57215 hom., cov: 33)
  • Exomes 𝑓: 0.84 (82616 hom.)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 6 publications found

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]

ADH5 Gene-Disease associations (from GenCC):

• AMED syndrome, digenic

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4	c.344+1269A>G		intron_variant	Intron 4 of 8	ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.344+1269A>G		intron_variant	Intron 4 of 8	1	NM_000671.4	ENSP00000296412.8

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131358 AN: 152140 Hom.: 57156 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.846

GnomAD4 exome AF: 0.837 AC: 196428 AN: 234550 Hom.: 82616 AF XY: 0.841 AC XY: 114248 AN XY: 135798

African (AFR) AF: 0.969 AC: 4668 AN: 4818

American (AMR) AF: 0.856 AC: 11984 AN: 13998

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 5484 AN: 7068

East Asian (EAS) AF: 0.998 AC: 6541 AN: 6552

South Asian (SAS) AF: 0.890 AC: 42125 AN: 47358

European-Finnish (FIN) AF: 0.785 AC: 8012 AN: 10206

Middle Eastern (MID) AF: 0.821 AC: 1564 AN: 1904

European-Non Finnish (NFE) AF: 0.812 AC: 106753 AN: 131508

Other (OTH) AF: 0.835 AC: 9297 AN: 11138

GnomAD4 genome AF: 0.863 AC: 131474 AN: 152258 Hom.: 57215 Cov.: 33 AF XY: 0.865 AC XY: 64407 AN XY: 74436

African (AFR) AF: 0.968 AC: 40241 AN: 41560

American (AMR) AF: 0.849 AC: 12979 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2661 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5165 AN: 5180

South Asian (SAS) AF: 0.899 AC: 4342 AN: 4828

European-Finnish (FIN) AF: 0.784 AC: 8297 AN: 10582

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55089 AN: 68026

Other (OTH) AF: 0.847 AC: 1791 AN: 2114

Alfa AF: 0.826 Hom.: 65108

Bravo AF: 0.872

Asia WGS AF: 0.934 AC: 3247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	18
DANN	Benign	0.57
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1154412; hg19: chr4-100001247;