rs13134042

chr4-95037876-G-Achr4-95037876-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001203.3(BMPR1B):c.-18+41742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,080 control chromosomes in the GnomAD database, including 3,109 homozygotes. 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 0.19 (3109 hom., cov: 32)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.29

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1B	NM_001203.3	c.-18+41742G>A		intron_variant		ENST00000515059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-18+41742G>A		intron_variant		1	NM_001203.3	P4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28157 AN: 151962 Hom.: 3107 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.185 AC: 28172 AN: 152080 Hom.: 3109 Cov.: 32 AF XY: 0.189 AC XY: 14074 AN XY: 74332

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.202

Alfa AF: 0.189 Hom.: 355

Bravo AF: 0.184

Asia WGS AF: 0.305 AC: 1061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.064
Dann	Benign	0.63

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

Other links and lift over

dbSNP: rs13134042; hg19: chr4-95959027;