4-99088587-G-C

Variant names:

• chr4-99088587-G-C
• rs1154401
• NM_000671.4:c.12+102C>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.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 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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)

ENSG00000246090 (HGNC:):

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 = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH5	NM_000671.4	c.12+102C>G		intron_variant	Intron 1 of 8	ENST00000296412.14	NP_000662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH5	ENST00000296412.14	c.12+102C>G		intron_variant	Intron 1 of 8	1	NM_000671.4	ENSP00000296412.8

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

African (AFR) AF: 0.675 AC: 16353 AN: 24240

American (AMR) AF: 0.765 AC: 18435 AN: 24104

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 11524 AN: 17600

East Asian (EAS) AF: 0.998 AC: 31978 AN: 32030

South Asian (SAS) AF: 0.836 AC: 44081 AN: 52760

European-Finnish (FIN) AF: 0.661 AC: 30969 AN: 46848

Middle Eastern (MID) AF: 0.714 AC: 3316 AN: 4644

European-Non Finnish (NFE) AF: 0.662 AC: 586489 AN: 885774

Other (OTH) AF: 0.697 AC: 32404 AN: 46486

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

African (AFR) AF: 0.672 AC: 27862 AN: 41436

American (AMR) AF: 0.720 AC: 11006 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2275 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5124 AN: 5136

South Asian (SAS) AF: 0.849 AC: 4089 AN: 4814

European-Finnish (FIN) AF: 0.674 AC: 7119 AN: 10560

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44400 AN: 67924

Other (OTH) AF: 0.677 AC: 1427 AN: 2108

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
PhyloP100		-1.1
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=14/86	disease causing (long InDel)

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: rs1154401; hg19: chr4-100009738;