rs251864

Variant names:

• chr19-39406653-A-G
• rs251864
• NM_003407.5:c.-252A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-39406653-A-G
• chr19-39406653-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003407.5(ZFP36):​c.-252A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 148,824 control chromosomes in the GnomAD database, including 12,646 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 0.40 (12646 hom., cov: 27)
• Consequence: ZFP36 NM_003407.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

Genes affected

ZFP36 (HGNC:12862): (ZFP36 ring finger protein) Enables several functions, including 14-3-3 protein binding activity; heat shock protein binding activity; and mRNA 3'-UTR AU-rich region binding activity. Involved in several processes, including cellular response to cytokine stimulus; cellular response to growth factor stimulus; and regulation of gene expression. Acts upstream of or within mRNA catabolic process. Located in cytoplasmic ribonucleoprotein granule; cytosol; and nucleus. Part of ribonucleoprotein complex. Colocalizes with RISC-loading complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP36	NM_003407.5	c.-252A>G		upstream_gene_variant		ENST00000597629.3	NP_003398.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP36	ENST00000597629.3	c.-252A>G		upstream_gene_variant		1	NM_003407.5	ENSP00000469647.2
ZFP36	ENST00000594442.2	c.-234A>G		upstream_gene_variant		5
ZFP36	ENST00000594045.2	c.-252A>G		upstream_gene_variant		3		ENSP00000472329.2
ZFP36	ENST00000652583.1	n.-205A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.398 AC: 59120 AN: 148714 Hom.: 12612 Cov.: 27

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.398 AC: 59206 AN: 148824 Hom.: 12646 Cov.: 27 AF XY: 0.401 AC XY: 29044 AN XY: 72394

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.430

Alfa AF: 0.360 Hom.: 1313

Bravo AF: 0.417

Asia WGS AF: 0.446 AC: 1545 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs251864; hg19: chr19-39897293;