4-99143082-G-C

Variant names:

• chr4-99143082-G-C
• rs2213035
• NM_000670.5:c.19-302C>G

Variant summary

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

The NM_000670.5(ADH4):​c.19-302C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 542,510 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: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ADH4 NM_000670.5 intron
• Scores: Splicing: ADA: 0.00006522
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.607
• Publications: 0 publications found

Genes affected

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]

ENSG00000246090 (HGNC:):

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=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH4	NM_000670.5	c.19-302C>G		intron_variant	Intron 1 of 8	ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.75+84C>G		intron_variant	Intron 2 of 9		NP_001293100.1
ADH4	NM_001306172.2	c.75+84C>G		intron_variant	Intron 2 of 9		NP_001293101.1
LOC100507053	NR_037884.1	n.679+9277G>C		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.19-302C>G		intron_variant	Intron 1 of 8	1	NM_000670.5	ENSP00000265512.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000184 AC: 1 AN: 542510 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 293934

African (AFR) AF: 0.0000642 AC: 1 AN: 15582

American (AMR) AF: 0.00 AC: 0 AN: 34364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19746

East Asian (EAS) AF: 0.00 AC: 0 AN: 31764

South Asian (SAS) AF: 0.00 AC: 0 AN: 61772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4010

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 312468

Other (OTH) AF: 0.00 AC: 0 AN: 30118

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.50
PhyloP100		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000065
dbscSNV1_RF	Benign	0.038
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: rs2213035; hg19: chr4-100064233;