rs1434536

Variant names:

• chr4-95154814-C-T
• rs1434536
• NM_001203.3:c.*141C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001203.3(BMPR1B):​c.*141C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,217,530 control chromosomes in the GnomAD database, including 174,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17468 hom., cov: 32)
  • Exomes 𝑓: 0.54 (157456 hom.)
• Consequence: BMPR1B NM_001203.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.887
• Publications: 49 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 4-95154814-C-T is Benign according to our data. Variant chr4-95154814-C-T is described in ClinVar as Benign. ClinVar VariationId is 350131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.*141C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.*141C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001203.3	ENSP00000426617.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69230 AN: 151930 Hom.: 17465 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.539 AC: 573933 AN: 1065482 Hom.: 157456 Cov.: 14 AF XY: 0.536 AC XY: 288841 AN XY: 538734

African (AFR) AF: 0.217 AC: 5393 AN: 24908

American (AMR) AF: 0.652 AC: 22975 AN: 35250

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 13454 AN: 22262

East Asian (EAS) AF: 0.390 AC: 13827 AN: 35426

South Asian (SAS) AF: 0.448 AC: 32247 AN: 72006

European-Finnish (FIN) AF: 0.574 AC: 24304 AN: 42370

Middle Eastern (MID) AF: 0.572 AC: 2746 AN: 4798

European-Non Finnish (NFE) AF: 0.556 AC: 434196 AN: 781424

Other (OTH) AF: 0.527 AC: 24791 AN: 47038

GnomAD4 genome AF: 0.456 AC: 69262 AN: 152048 Hom.: 17468 Cov.: 32 AF XY: 0.459 AC XY: 34121 AN XY: 74308

African (AFR) AF: 0.226 AC: 9359 AN: 41488

American (AMR) AF: 0.588 AC: 8982 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3472

East Asian (EAS) AF: 0.387 AC: 1994 AN: 5152

South Asian (SAS) AF: 0.438 AC: 2109 AN: 4816

European-Finnish (FIN) AF: 0.579 AC: 6114 AN: 10556

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36979 AN: 67976

Other (OTH) AF: 0.486 AC: 1028 AN: 2114

Alfa AF: 0.516 Hom.: 56163

Bravo AF: 0.450

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24339876, 21556765, 19738052) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Brachydactyly Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Type A2 brachydactyly;C4225404:Acromesomelic dysplasia 3 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		0.89
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: rs1434536; hg19: chr4-96075965; COSMIC: COSV52775666; COSMIC: COSV52775666;