rs147994992

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004864.4(GDF15):c.350C>A(p.Ala117Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,611,608 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 5 hom. )

Consequence

GDF15
NM_004864.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.362

Variant links:

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]

GDF15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041142404).

BP6

Variant 19-18388358-C-A is Benign according to our data. Variant chr19-18388358-C-A is described in ClinVar as [Benign]. Clinvar id is 780552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF15	NM_004864.4 link	c.350C>A	p.Ala117Asp	missense_variant	Exon 2 of 2	ENST00000252809.3	NP_004855.2	Q99988

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GDF15	ENST00000252809.3 link	c.350C>A	p.Ala117Asp	missense_variant	Exon 2 of 2	1	NM_004864.4	ENSP00000252809.3	Q99988
GDF15	ENST00000595973.3 link	c.350C>A	p.Ala117Asp	missense_variant	Exon 3 of 3	5		ENSP00000470531.3	Q99988A0A0A0MTT8
GDF15	ENST00000597765.2 link	c.350C>A	p.Ala117Asp	missense_variant	Exon 3 of 3	4		ENSP00000469819.2	Q99988
GDF15	ENST00000594925.1 link	n.168C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

382

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000755

AC:

183

AN:

242250

Hom.:

AF XY:

0.000571

AC XY:

AN XY:

133124

show subpopulations

Gnomad AFR exome

AF:

0.00970

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000273

AC:

399

AN:

1459272

Hom.:

Cov.:

AF XY:

0.000247

AC XY:

179

AN XY:

725982

show subpopulations

Gnomad4 AFR exome

AF:

0.00844

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000913

GnomAD4 genome

AF:

0.00251

AC:

383

AN:

152336

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

178

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00813

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.00308

ESP6500AA

AF:

0.00554

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000736

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.21

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.52

M_CAP

Benign

0.048

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.93

REVEL

Benign

0.16

Sift

Benign

0.091

Sift4G

Benign

0.48

Polyphen

0.0010

Vest4

0.21

MVP

0.56

MPC

0.95

ClinPred

0.0022

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.59

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over