4-99088976-C-T

Variant names:

• chr4-99088976-C-T
• rs2851301
• ENST00000500358.6:n.120C>T

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.120C>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 0.38 in 434,456 control chromosomes in the GnomAD database, including 35,326 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 (10212 hom., cov: 33)
  • Exomes 𝑓: 0.40 (25114 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 5 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.120C>T		non_coding_transcript_exon	Exon 1 of 10
	ADH5	NM_000671.4	MANE Select	c.-276G>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.120C>T		non_coding_transcript_exon	Exon 1 of 10
	ENSG00000246090	ENST00000499178.3	TSL:3	n.107C>T		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000246090	ENST00000661393.1		n.117C>T		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51188 AN: 151760 Hom.: 10206 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.403 AC: 113952 AN: 282576 Hom.: 25114 Cov.: 0 AF XY: 0.409 AC XY: 60207 AN XY: 147168

African (AFR) AF: 0.132 AC: 990 AN: 7506

American (AMR) AF: 0.327 AC: 2995 AN: 9168

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 3859 AN: 9730

East Asian (EAS) AF: 0.116 AC: 2599 AN: 22490

South Asian (SAS) AF: 0.513 AC: 9275 AN: 18066

European-Finnish (FIN) AF: 0.444 AC: 10292 AN: 23188

Middle Eastern (MID) AF: 0.453 AC: 602 AN: 1330

European-Non Finnish (NFE) AF: 0.441 AC: 76445 AN: 173414

Other (OTH) AF: 0.390 AC: 6895 AN: 17684

GnomAD4 genome AF: 0.337 AC: 51194 AN: 151880 Hom.: 10212 Cov.: 33 AF XY: 0.340 AC XY: 25223 AN XY: 74214

African (AFR) AF: 0.134 AC: 5553 AN: 41514

American (AMR) AF: 0.328 AC: 5017 AN: 15276

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

East Asian (EAS) AF: 0.129 AC: 668 AN: 5168

South Asian (SAS) AF: 0.511 AC: 2458 AN: 4812

European-Finnish (FIN) AF: 0.449 AC: 4717 AN: 10494

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

European-Non Finnish (NFE) AF: 0.445 AC: 30198 AN: 67834

Other (OTH) AF: 0.352 AC: 744 AN: 2112

Alfa AF: 0.388 Hom.: 12433

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	1.1
DANN	Benign	0.88
PhyloP100		-1.4
PromoterAI		-0.066	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2851301; hg19: chr4-100010127;