rs896992

Variant names:

• chr4-99081221-C-A
• rs896992
• NM_000671.4:c.344+144G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-99081221-C-A
• chr4-99081221-C-G
• chr4-99081221-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000671.4(ADH5):​c.344+144G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000545 in 366,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 26)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ADH5 NM_000671.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000671.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	NM_000671.4	MANE Select	c.344+144G>T		intron	N/A	NP_000662.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH5	ENST00000296412.14	TSL:1 MANE Select	c.344+144G>T		intron	N/A	ENSP00000296412.8
	ADH5	ENST00000503130.5	TSL:3	c.305+144G>T		intron	N/A	ENSP00000427049.1
	ADH5	ENST00000626055.2	TSL:5	c.*31+144G>T		intron	N/A	ENSP00000487496.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000545 AC: 2 AN: 366704 Hom.: 0 AF XY: 0.00000496 AC XY: 1 AN XY: 201758

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7416

American (AMR) AF: 0.00 AC: 0 AN: 12270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12186

East Asian (EAS) AF: 0.00 AC: 0 AN: 18086

South Asian (SAS) AF: 0.00 AC: 0 AN: 45366

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1438

European-Non Finnish (NFE) AF: 0.00000933 AC: 2 AN: 214370

Other (OTH) AF: 0.00 AC: 0 AN: 18612

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-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

Other links and lift over

dbSNP: rs896992; hg19: chr4-100002372;