chr4-99144442-T-C

Variant names:

• chr4-99144442-T-C
• rs1800761
• ENST00000500358.6:n.680-10103T>C

Variant summary

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

The ENST00000500358.6(ENSG00000246090):​n.680-10103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 422,244 control chromosomes in the GnomAD database, including 126,498 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 0.77 (45546 hom., cov: 32)
  • Exomes 𝑓: 0.76 (80952 hom.)
• Consequence: ENSG00000246090 ENST00000500358.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 7 publications found

Genes affected

ENSG00000246090 (HGNC:):

ADH4 (HGNC:252): (alcohol dehydrogenase 4 (class II), pi polypeptide) This gene encodes class II alcohol dehydrogenase 4 pi subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.808 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100507053	NR_037884.1		n.680-10103T>C		intron	N/A
	ADH4	NM_000670.5	MANE Select	c.-220A>G		upstream_gene	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.-311A>G		upstream_gene	N/A	NP_001293100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000246090	ENST00000500358.6	TSL:1	n.680-10103T>C		intron	N/A
	ADH4	ENST00000504581.1	TSL:3	n.170-1662A>G		intron	N/A
	ENSG00000246090	ENST00000661393.1		n.676+10637T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116470 AN: 152018 Hom.: 45515 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.756 AC: 204143 AN: 270108 Hom.: 80952 AF XY: 0.756 AC XY: 105400 AN XY: 139448

African (AFR) AF: 0.726 AC: 5594 AN: 7700

American (AMR) AF: 0.831 AC: 7888 AN: 9488

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 7626 AN: 9518

East Asian (EAS) AF: 0.262 AC: 6282 AN: 24006

South Asian (SAS) AF: 0.680 AC: 6371 AN: 9374

European-Finnish (FIN) AF: 0.826 AC: 18249 AN: 22094

Middle Eastern (MID) AF: 0.767 AC: 1034 AN: 1348

European-Non Finnish (NFE) AF: 0.814 AC: 137923 AN: 169390

Other (OTH) AF: 0.766 AC: 13176 AN: 17190

GnomAD4 genome AF: 0.766 AC: 116549 AN: 152136 Hom.: 45546 Cov.: 32 AF XY: 0.763 AC XY: 56707 AN XY: 74368

African (AFR) AF: 0.723 AC: 30002 AN: 41486

American (AMR) AF: 0.819 AC: 12522 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1378 AN: 5184

South Asian (SAS) AF: 0.677 AC: 3266 AN: 4826

European-Finnish (FIN) AF: 0.830 AC: 8773 AN: 10572

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55309 AN: 67998

Other (OTH) AF: 0.780 AC: 1645 AN: 2110

Alfa AF: 0.791 Hom.: 5936

Bravo AF: 0.763

Asia WGS AF: 0.590 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.98
DANN	Benign	0.40
PhyloP100		-1.5
PromoterAI		-0.065	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1800761; hg19: chr4-100065593;