rs201445214

Variant names:

• chr19-18386195-C-T
• rs201445214
• NM_004864.4:c.6C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-18386195-C-T
• chr19-18386195-C-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004864.4(GDF15):​c.6C>T​(p.Pro2Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,610,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: GDF15 NM_004864.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20
• Publications: 2 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-18386195-C-T is Benign according to our data. Variant chr19-18386195-C-T is described in ClinVar as Benign. ClinVar VariationId is 716361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004864.4. 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
	GDF15	NM_004864.4	MANE Select	c.6C>T	p.Pro2Pro	synonymous	Exon 1 of 2	NP_004855.2	Q99988

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF15	ENST00000252809.3	TSL:1 MANE Select	c.6C>T	p.Pro2Pro	synonymous	Exon 1 of 2	ENSP00000252809.3	Q99988
	GDF15	ENST00000595973.3	TSL:5	c.6C>T	p.Pro2Pro	synonymous	Exon 2 of 3	ENSP00000470531.3	Q99988
	GDF15	ENST00000597765.2	TSL:4	c.6C>T	p.Pro2Pro	synonymous	Exon 2 of 3	ENSP00000469819.2	Q99988

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000500 AC: 125 AN: 249894 AF XY: 0.000363

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00349

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000622

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.000162 AC: 236 AN: 1458684 Hom.: 0 Cov.: 29 AF XY: 0.000153 AC XY: 111 AN XY: 725404

African (AFR) AF: 0.0000300 AC: 1 AN: 33388

American (AMR) AF: 0.00222 AC: 99 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00284 AC: 74 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4342

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1110878

Other (OTH) AF: 0.000332 AC: 20 AN: 60196

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74468

African (AFR) AF: 0.0000722 AC: 3 AN: 41562

American (AMR) AF: 0.00216 AC: 33 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000450 Hom.: 0

Bravo AF: 0.000892

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.7
DANN	Benign	0.79
PhyloP100		-1.2
PromoterAI		-0.033	Neutral

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: rs201445214; hg19: chr19-18497005;