rs141691706

Positions:

• chr4-95125083-T-A
• chr4-95125083-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001203.3(BMPR1B):​c.547T>A​(p.Ser183Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: BMPR1B NM_001203.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15

Genes affected

BMPR1B (HGNC:1077): (bone morphogenetic protein receptor type 1B) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38353318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.547T>A	p.Ser183Thr	missense_variant	8/13	ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.547T>A	p.Ser183Thr	missense_variant	8/13	1	NM_001203.3	ENSP00000426617.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Uncertain	0.56	D;D;.;D;D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	.;.;D;.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.38	T;T;T;T;T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	1.8	L;L;.;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.44	N;N;N;N;N
REVEL	Uncertain	0.53
Sift	Benign	0.43	T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.98	D;D;.;D;D
Vest4		0.49
MutPred		0.32		Loss of phosphorylation at S183 (P = 0.0727);Loss of phosphorylation at S183 (P = 0.0727);.;Loss of phosphorylation at S183 (P = 0.0727);Loss of phosphorylation at S183 (P = 0.0727);
MVP		0.75
MPC		0.039
ClinPred		0.70	D
GERP RS		5.6
Varity_R		0.56
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs141691706; hg19: chr4-96046234;