rs1227732

Variant names:

• chr19-18387998-T-A
• rs1227732
• NM_004864.4:c.278-288T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-18387998-T-A
• chr19-18387998-T-C
• chr19-18387998-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004864.4(GDF15):​c.278-288T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0000066 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• Consequence: GDF15 NM_004864.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 6 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF15	NM_004864.4	c.278-288T>A		intron_variant	Intron 1 of 1	ENST00000252809.3	NP_004855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF15	ENST00000252809.3	c.278-288T>A		intron_variant	Intron 1 of 1	1	NM_004864.4	ENSP00000252809.3
GDF15	ENST00000595973.3	c.278-288T>A		intron_variant	Intron 2 of 2	5		ENSP00000470531.3
GDF15	ENST00000597765.2	c.278-288T>A		intron_variant	Intron 2 of 2	4		ENSP00000469819.2
GDF15	ENST00000594925.1	n.96-288T>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151462 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000660 AC: 1 AN: 151462 Hom.: 0 Cov.: 27 AF XY: 0.0000135 AC XY: 1 AN XY: 73936

African (AFR) AF: 0.00 AC: 0 AN: 41084

American (AMR) AF: 0.00 AC: 0 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67914

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 2787

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.5
DANN	Benign	0.95
PhyloP100		-0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1227732; hg19: chr19-18498808;