19-39406653-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP36	NM_003407.5	MANE Select	c.-252A>G		upstream_gene	N/A	NP_003398.3	P26651

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP36	ENST00000597629.3	TSL:1 MANE Select	c.-252A>G		upstream_gene	N/A	ENSP00000469647.2	P26651
	ZFP36	ENST00000918416.1		c.-252A>G		upstream_gene	N/A	ENSP00000588475.1
	ZFP36	ENST00000594045.2	TSL:3	c.-252A>G		upstream_gene	N/A	ENSP00000472329.2	M0R252

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

African (AFR) AF: 0.527 AC: 21318 AN: 40420

American (AMR) AF: 0.503 AC: 7518 AN: 14952

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1219 AN: 3442

East Asian (EAS) AF: 0.283 AC: 1387 AN: 4906

South Asian (SAS) AF: 0.573 AC: 2699 AN: 4708

European-Finnish (FIN) AF: 0.235 AC: 2335 AN: 9918

Middle Eastern (MID) AF: 0.486 AC: 140 AN: 288

European-Non Finnish (NFE) AF: 0.318 AC: 21400 AN: 67242

Other (OTH) AF: 0.430 AC: 885 AN: 2056

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.57
PhyloP100		-0.25
PromoterAI		-0.073	Neutral

Splicing

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

Other links and lift over

dbSNP: rs251864; hg19: chr19-39897293;