rs10009145

Positions:

• chr4-99126778-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADH4	NM_000670.5	c.980-46C>T		intron_variant		ENST00000265512.12	NP_000661.2
ADH4	NM_001306171.2	c.1037-46C>T		intron_variant			NP_001293100.1
ADH4	NM_001306172.2	c.1037-46C>T		intron_variant			NP_001293101.1
LOC100507053	NR_037884.1	n.429-6777G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADH4	ENST00000265512.12	c.980-46C>T		intron_variant		1	NM_000670.5	ENSP00000265512.7

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

GnomAD3 exomes AF: 0.394 AC: 93292 AN: 236856 Hom.: 20264 AF XY: 0.408 AC XY: 52424 AN XY: 128446

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 SAS exome AF: 0.526

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

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.519

Gnomad4 FIN exome AF: 0.463

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.422

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.356

Alfa AF: 0.401 Hom.: 2433

Bravo AF: 0.314

Asia WGS AF: 0.361 AC: 1256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs10009145; hg19: chr4-100047929; COSMIC: COSV55501820; COSMIC: COSV55501820;