rs4145993

Positions:

• chr4-94995128-T-C

Variant summary

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

The NM_001203.3(BMPR1B):​c.-112-912T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,046 control chromosomes in the GnomAD database, including 40,645 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 0.72 (40645 hom., cov: 31)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1B	NM_001203.3	c.-112-912T>C		intron_variant		ENST00000515059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-112-912T>C		intron_variant		1	NM_001203.3	P4
BMPR1B	ENST00000672698.1	c.-112-912T>C		intron_variant				P4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109446 AN: 151928 Hom.: 40623 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.720 AC: 109519 AN: 152046 Hom.: 40645 Cov.: 31 AF XY: 0.722 AC XY: 53648 AN XY: 74320

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.717

Alfa AF: 0.749 Hom.: 5412

Bravo AF: 0.714

Asia WGS AF: 0.787 AC: 2735 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.55

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: rs4145993; hg19: chr4-95916279;