rs1054564

Variant names:

• chr19-18389005-G-A
• rs1054564
• NM_004864.4:c.*70G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18389005-G-A
• chr19-18389005-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004864.4(GDF15):​c.*70G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 921,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: GDF15 NM_004864.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849
• Publications: 0 publications found

Genes affected

GDF15 (HGNC:30142): (growth differentiation factor 15) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The protein is expressed in a broad range of cell types, acts as a pleiotropic cytokine and is involved in the stress response program of cells after cellular injury. Increased protein levels are associated with disease states such as tissue hypoxia, inflammation, acute injury and oxidative stress. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF15	NM_004864.4	c.*70G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000252809.3	NP_004855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF15	ENST00000252809.3	c.*70G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_004864.4	ENSP00000252809.3
GDF15	ENST00000595973.3	c.*70G>A		downstream_gene_variant		5		ENSP00000470531.3
GDF15	ENST00000597765.2	c.*70G>A		downstream_gene_variant		4		ENSP00000469819.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 921564 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 465050

African (AFR) AF: 0.00 AC: 0 AN: 21666

American (AMR) AF: 0.00 AC: 0 AN: 30168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17694

East Asian (EAS) AF: 0.00 AC: 0 AN: 35472

South Asian (SAS) AF: 0.00 AC: 0 AN: 59444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4154

European-Non Finnish (NFE) AF: 0.00000148 AC: 1 AN: 676286

Other (OTH) AF: 0.00 AC: 0 AN: 41872

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.85
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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: rs1054564; hg19: chr19-18499815;