4-95051944-GCTTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001203.3(BMPR1B):c.-17-52461_-17-52458del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,094 control chromosomes in the GnomAD database, including 669 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.090 (669 hom., cov: 31)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.937

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 -10 ACMG points.

• BP6: Variant 4-95051944-GCTTT-G is Benign according to our data. Variant chr4-95051944-GCTTT-G is described in ClinVar as [Benign]. Clinvar id is 1302826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1B	NM_001203.3	c.-17-52461_-17-52458del		intron_variant		ENST00000515059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-17-52461_-17-52458del		intron_variant		1	NM_001203.3	P4

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13622 AN: 151976 Hom.: 666 Cov.: 31

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0896 AC: 13634 AN: 152094 Hom.: 669 Cov.: 31 AF XY: 0.0896 AC XY: 6665 AN XY: 74372

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0450

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0935 Hom.: 78

Bravo AF: 0.0871

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs5860387; hg19: chr4-95973095;