4-99088977-C-T

Variant names:

• chr4-99088977-C-T
• rs2602899
• ENST00000500358.6:n.121C>T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.121C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 427,614 control chromosomes in the GnomAD database, including 34,563 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 0.34 (10211 hom., cov: 33)
  • Exomes 𝑓: 0.40 (24352 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923
• Publications: 4 publications found

Genes affected

ENSG00000246090 (HGNC:):

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500358.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100507053	NR_037884.1		n.121C>T		non_coding_transcript_exon	Exon 1 of 10
	ADH5	NM_000671.4	MANE Select	c.-277G>A		upstream_gene	N/A	NP_000662.3	P11766

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.121C>T		non_coding_transcript_exon	Exon 1 of 10
	ENSG00000246090	ENST00000499178.3	TSL:3	n.108C>T		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000246090	ENST00000661393.1		n.118C>T		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51184 AN: 151750 Hom.: 10205 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.401 AC: 110516 AN: 275744 Hom.: 24352 Cov.: 0 AF XY: 0.406 AC XY: 58247 AN XY: 143372

African (AFR) AF: 0.132 AC: 973 AN: 7398

American (AMR) AF: 0.322 AC: 2855 AN: 8866

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 3803 AN: 9598

East Asian (EAS) AF: 0.115 AC: 2570 AN: 22316

South Asian (SAS) AF: 0.505 AC: 8278 AN: 16390

European-Finnish (FIN) AF: 0.443 AC: 10091 AN: 22794

Middle Eastern (MID) AF: 0.449 AC: 587 AN: 1306

European-Non Finnish (NFE) AF: 0.440 AC: 74627 AN: 169758

Other (OTH) AF: 0.389 AC: 6732 AN: 17318

GnomAD4 genome AF: 0.337 AC: 51190 AN: 151870 Hom.: 10211 Cov.: 33 AF XY: 0.340 AC XY: 25218 AN XY: 74204

African (AFR) AF: 0.134 AC: 5554 AN: 41508

American (AMR) AF: 0.328 AC: 5018 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.129 AC: 667 AN: 5166

South Asian (SAS) AF: 0.511 AC: 2457 AN: 4812

European-Finnish (FIN) AF: 0.450 AC: 4717 AN: 10492

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30196 AN: 67834

Other (OTH) AF: 0.352 AC: 742 AN: 2108

Alfa AF: 0.345 Hom.: 1866

Bravo AF: 0.313

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.4
DANN	Benign	0.89
PhyloP100		-0.92
PromoterAI		0.014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2602899;

hg19: chr4-100010128;