14-68787474-C-T

Variant names:

• chr14-68787474-C-T
• rs4902647
• NM_004926.4:c.*2059G>A

Variant summary

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

The NM_004926.4(ZFP36L1):​c.*2059G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,026 control chromosomes in the GnomAD database, including 15,781 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 0.45 (15781 hom., cov: 32)
• Consequence: ZFP36L1 NM_004926.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 57 publications found

Genes affected

ZFP36L1 (HGNC:1107): (ZFP36 ring finger protein like 1) This gene is a member of the TIS11 family of early response genes, which are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. This gene is well conserved across species and has a promoter that contains motifs seen in other early-response genes. The encoded protein contains a distinguishing putative zinc finger domain with a repeating cys-his motif. This putative nuclear transcription factor most likely functions in regulating the response to growth factors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000289583 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP36L1	NM_004926.4	c.*2059G>A		downstream_gene_variant		ENST00000439696.3	NP_004917.2
ZFP36L1	NM_001244701.1	c.*2059G>A		downstream_gene_variant			NP_001231630.1
ZFP36L1	NM_001244698.2	c.*1342G>A		downstream_gene_variant			NP_001231627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP36L1	ENST00000439696.3	c.*2059G>A		downstream_gene_variant		1	NM_004926.4	ENSP00000388402.2
ENSG00000289583	ENST00000768259.1	n.-95G>A		upstream_gene_variant
ZFP36L1	ENST00000336440.5	c.*1342G>A		downstream_gene_variant		2		ENSP00000337386.3
ZFP36L1	ENST00000555997.1	n.*186G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68175 AN: 151906 Hom.: 15769 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.449 AC: 68230 AN: 152026 Hom.: 15781 Cov.: 32 AF XY: 0.453 AC XY: 33694 AN XY: 74324

African (AFR) AF: 0.355 AC: 14731 AN: 41454

American (AMR) AF: 0.511 AC: 7809 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1667 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3460 AN: 5162

South Asian (SAS) AF: 0.488 AC: 2354 AN: 4826

European-Finnish (FIN) AF: 0.495 AC: 5227 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31548 AN: 67948

Other (OTH) AF: 0.470 AC: 989 AN: 2106

Alfa AF: 0.457 Hom.: 48422

Bravo AF: 0.449

Asia WGS AF: 0.570 AC: 1977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs4902647; hg19: chr14-69254191;