rs17563

Variant names:

• chr14-53950804-A-C
• NM_001202.6:c.455T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-53950804-A-C
• chr14-53950804-A-G
• chr14-53950804-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001202.6(BMP4):​c.455T>G​(p.Val152Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V152A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BMP4 NM_001202.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23

Genes affected

BMP4 (HGNC:1071): (bone morphogenetic protein 4) 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. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.455T>G	p.Val152Gly	missense_variant	Exon 4 of 4	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.455T>G	p.Val152Gly	missense_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Uncertain	0.69	D;D;D;D;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	.;.;D;.;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.71	D;D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.4	M;M;M;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.13	T;T;T;T;D
Sift4G	Benign	0.36	T;T;T;T;.
Polyphen		0.28	B;B;B;B;.
Vest4		0.33
MutPred		0.40		Loss of stability (P = 6e-04);Loss of stability (P = 6e-04);Loss of stability (P = 6e-04);Loss of stability (P = 6e-04);.;
MVP		0.73
MPC		0.76
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.41
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-54417522;