19-39408027-C-T

Variant names:

• chr19-39408027-C-T
• rs3746083
• NM_003407.5:c.309C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_003407.5(ZFP36):​c.309C>T​(p.Arg103Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0397 in 1,613,562 control chromosomes in the GnomAD database, including 1,318 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 0.038 (116 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1202 hom.)
• Consequence: ZFP36 NM_003407.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0377 (5741/152282) while in subpopulation NFE AF = 0.0405 (2751/68006). AF 95% confidence interval is 0.0392. There are 116 homozygotes in GnomAd4. There are 2756 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 116 gene

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.309C>T	p.Arg103Arg	synonymous	Exon 2 of 2	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.309C>T	p.Arg103Arg	synonymous	Exon 2 of 2	ENSP00000469647.2	P26651
	ZFP36	ENST00000594045.2	TSL:3	c.*292C>T		3_prime_UTR	Exon 2 of 2	ENSP00000472329.2	M0R252
	ZFP36	ENST00000918416.1		c.25-61C>T		intron	N/A	ENSP00000588475.1

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5720 AN: 152164 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0468

GnomAD2 exomes AF: 0.0351 AC: 8734 AN: 249002 AF XY: 0.0356

Gnomad AFR exome AF: 0.0374

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.0546

Gnomad EAS exome AF: 0.0401

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.0401

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0399 AC: 58264 AN: 1461280 Hom.: 1202 Cov.: 31 AF XY: 0.0394 AC XY: 28661 AN XY: 727000

African (AFR) AF: 0.0406 AC: 1360 AN: 33478

American (AMR) AF: 0.0251 AC: 1122 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 1425 AN: 26130

East Asian (EAS) AF: 0.0346 AC: 1372 AN: 39698

South Asian (SAS) AF: 0.0303 AC: 2616 AN: 86256

European-Finnish (FIN) AF: 0.0179 AC: 944 AN: 52858

Middle Eastern (MID) AF: 0.0499 AC: 288 AN: 5768

European-Non Finnish (NFE) AF: 0.0419 AC: 46623 AN: 1111980

Other (OTH) AF: 0.0416 AC: 2514 AN: 60388

GnomAD4 genome AF: 0.0377 AC: 5741 AN: 152282 Hom.: 116 Cov.: 32 AF XY: 0.0370 AC XY: 2756 AN XY: 74458

African (AFR) AF: 0.0382 AC: 1586 AN: 41562

American (AMR) AF: 0.0347 AC: 531 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3472

East Asian (EAS) AF: 0.0380 AC: 196 AN: 5162

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4826

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10626

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0405 AC: 2751 AN: 68006

Other (OTH) AF: 0.0463 AC: 98 AN: 2116

Alfa AF: 0.0337 Hom.: 60

Bravo AF: 0.0398

Asia WGS AF: 0.0400 AC: 142 AN: 3478

EpiCase AF: 0.0442

EpiControl AF: 0.0464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.2
DANN	Benign	0.87
PhyloP100		0.17
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: rs3746083; hg19: chr19-39898667; COSMIC: COSV50527647; COSMIC: COSV50527647;