chr4-99126778-G-A

Variant names:

• chr4-99126778-G-A
• rs10009145
• NM_000670.5:c.980-46C>T

Variant summary

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

The NM_000670.5(ADH4):​c.980-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,534,828 control chromosomes in the GnomAD database, including 146,925 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 (10412 hom., cov: 32)
  • Exomes 𝑓: 0.44 (136513 hom.)
• Consequence: ADH4 NM_000670.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 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.980-46C>T		intron	N/A	NP_000661.2
	ADH4	NM_001306171.2		c.1037-46C>T		intron	N/A	NP_001293100.1
	ADH4	NM_001306172.2		c.1037-46C>T		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.980-46C>T		intron	N/A	ENSP00000265512.7
	ENSG00000246090	ENST00000500358.6	TSL:1	n.429-6777G>A		intron	N/A
	ADH4	ENST00000505590.5	TSL:5	c.1037-46C>T		intron	N/A	ENSP00000425416.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51551 AN: 151956 Hom.: 10409 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.394 AC: 93292 AN: 236856 AF XY: 0.408

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.435 AC: 601934 AN: 1382754 Hom.: 136513 Cov.: 28 AF XY: 0.438 AC XY: 298457 AN XY: 681126

African (AFR) AF: 0.122 AC: 3932 AN: 32276

American (AMR) AF: 0.329 AC: 13770 AN: 41884

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 9692 AN: 23786

East Asian (EAS) AF: 0.105 AC: 4099 AN: 38908

South Asian (SAS) AF: 0.519 AC: 38695 AN: 74618

European-Finnish (FIN) AF: 0.463 AC: 22746 AN: 49154

Middle Eastern (MID) AF: 0.443 AC: 2398 AN: 5418

European-Non Finnish (NFE) AF: 0.455 AC: 482712 AN: 1060052

Other (OTH) AF: 0.422 AC: 23890 AN: 56658

GnomAD4 genome AF: 0.339 AC: 51555 AN: 152074 Hom.: 10412 Cov.: 32 AF XY: 0.342 AC XY: 25437 AN XY: 74348

African (AFR) AF: 0.134 AC: 5559 AN: 41506

American (AMR) AF: 0.330 AC: 5035 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3470

East Asian (EAS) AF: 0.117 AC: 607 AN: 5174

South Asian (SAS) AF: 0.498 AC: 2400 AN: 4824

European-Finnish (FIN) AF: 0.464 AC: 4893 AN: 10550

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

European-Non Finnish (NFE) AF: 0.448 AC: 30457 AN: 67960

Other (OTH) AF: 0.356 AC: 751 AN: 2112

Alfa AF: 0.394 Hom.: 2443

Bravo AF: 0.314

Asia WGS AF: 0.361 AC: 1256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		-0.063
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: rs10009145; hg19: chr4-100047929; COSMIC: COSV55501820; COSMIC: COSV55501820;