rs2679757

Variant names:

• chr8-102858590-A-G
• rs2679757
• NM_148174.4:c.-233-440T>C

Variant summary

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

The NM_148174.4(AZIN1):​c.-233-440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,068 control chromosomes in the GnomAD database, including 11,696 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 0.38 (11696 hom., cov: 32)
• Consequence: AZIN1 NM_148174.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 8 publications found

Genes affected

AZIN1 (HGNC:16432): (antizyme inhibitor 1) The protein encoded by this gene belongs to the antizyme inhibitor family, which plays a role in cell growth and proliferation by maintaining polyamine homeostasis within the cell. Antizyme inhibitors are homologs of ornithine decarboxylase (ODC, the key enzyme in polyamine biosynthesis) that have lost the ability to decarboxylase ornithine; however, retain the ability to bind to antizymes. Antizymes negatively regulate intracellular polyamine levels by binding to ODC and targeting it for degradation, as well as by inhibiting polyamine uptake. Antizyme inhibitors function as positive regulators of polyamine levels by sequestering antizymes and neutralizing their effect. This gene encodes antizyme inhibitor 1, the first member of this gene family that is ubiquitously expressed, and is localized in the nucleus and cytoplasm. Overexpression of antizyme inhibitor 1 gene has been associated with increased proliferation, cellular transformation and tumorigenesis. Gene knockout studies showed that homozygous mutant mice lacking functional antizyme inhibitor 1 gene died at birth with abnormal liver morphology. RNA editing of this gene, predominantly in the liver tissue, has been linked to the progression of hepatocellular carcinoma. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2014]

ENSG00000289653 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AZIN1	NM_148174.4	c.-233-440T>C		intron_variant	Intron 1 of 11	ENST00000337198.10	NP_680479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AZIN1	ENST00000337198.10	c.-233-440T>C		intron_variant	Intron 1 of 11	1	NM_148174.4	ENSP00000337180.5
ENSG00000289653	ENST00000695129.1	c.55-440T>C		intron_variant	Intron 1 of 1			ENSP00000511718.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57145 AN: 151950 Hom.: 11703 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.376 AC: 57153 AN: 152068 Hom.: 11696 Cov.: 32 AF XY: 0.381 AC XY: 28344 AN XY: 74330

African (AFR) AF: 0.217 AC: 9018 AN: 41490

American (AMR) AF: 0.457 AC: 6978 AN: 15272

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

East Asian (EAS) AF: 0.234 AC: 1214 AN: 5178

South Asian (SAS) AF: 0.460 AC: 2218 AN: 4818

European-Finnish (FIN) AF: 0.508 AC: 5363 AN: 10562

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29573 AN: 67966

Other (OTH) AF: 0.390 AC: 822 AN: 2110

Alfa AF: 0.396 Hom.: 1661

Bravo AF: 0.362

Asia WGS AF: 0.390 AC: 1357 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.20
PromoterAI		0.0061	Neutral
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: rs2679757; hg19: chr8-103870818;