rs4490463

Variant names:

• chr4-94811194-G-A
• rs4490463
• NM_001203.3:c.-183+53126G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-94811194-G-A
• chr4-94811194-G-C
• chr4-94811194-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001203.3(BMPR1B):​c.-183+53126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,032 control chromosomes in the GnomAD database, including 24,800 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 0.57 (24800 hom., cov: 33)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 3 publications found

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]

BMPR1B Gene-Disease associations (from GenCC):

• brachydactyly type A2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• acromesomelic dysplasia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• brachydactyly

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• brachydactyly type A1D

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• brachydactyly type A1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acromesomelic dysplasia 2A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• acromesomelic dysplasia 2B

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pulmonary arterial hypertension

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.-183+53126G>A		intron_variant	Intron 1 of 12	ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-183+53126G>A		intron_variant	Intron 1 of 12	1	NM_001203.3	ENSP00000426617.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86392 AN: 151912 Hom.: 24766 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.569 AC: 86461 AN: 152032 Hom.: 24800 Cov.: 33 AF XY: 0.572 AC XY: 42482 AN XY: 74324

African (AFR) AF: 0.483 AC: 20019 AN: 41460

American (AMR) AF: 0.647 AC: 9880 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2337 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3068 AN: 5166

South Asian (SAS) AF: 0.546 AC: 2635 AN: 4828

European-Finnish (FIN) AF: 0.606 AC: 6402 AN: 10556

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40217 AN: 67962

Other (OTH) AF: 0.583 AC: 1230 AN: 2110

Alfa AF: 0.588 Hom.: 6997

Bravo AF: 0.567

Asia WGS AF: 0.573 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.36
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4490463; hg19: chr4-95732345;