chr4-99125672-A-G

Variant names:

• chr4-99125672-A-G
• rs29001229
• NM_000670.5:c.1118+922T>C

Variant summary

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

The NM_000670.5(ADH4):​c.1118+922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,022 control chromosomes in the GnomAD database, including 4,054 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 0.21 (4054 hom., cov: 32)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000670.5. 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
	ADH4	NM_000670.5	MANE Select	c.1118+922T>C		intron	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.1175+922T>C		intron	N/A	NP_001293100.1
	ADH4	NM_001306172.2		c.1175+922T>C		intron	N/A	NP_001293101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH4	ENST00000265512.12	TSL:1 MANE Select	c.1118+922T>C		intron	N/A	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.429-7883A>G		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.1175+922T>C		intron	N/A	ENSP00000425416.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32052 AN: 151904 Hom.: 4056 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32055 AN: 152022 Hom.: 4054 Cov.: 32 AF XY: 0.203 AC XY: 15103 AN XY: 74292

African (AFR) AF: 0.109 AC: 4540 AN: 41476

American (AMR) AF: 0.209 AC: 3185 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5170

South Asian (SAS) AF: 0.116 AC: 561 AN: 4818

European-Finnish (FIN) AF: 0.234 AC: 2473 AN: 10558

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19371 AN: 67948

Other (OTH) AF: 0.238 AC: 503 AN: 2114

Alfa AF: 0.235 Hom.: 624

Bravo AF: 0.204

Asia WGS AF: 0.0680 AC: 239 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	2.2
DANN	Benign	0.75
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs29001229; hg19: chr4-100046823;