4-95104151-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001203.3(BMPR1B):c.-17-257T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 151,806 control chromosomes in the GnomAD database, including 53,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.84 (53262 hom., cov: 31)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-95104151-T-G is Benign according to our data. Variant chr4-95104151-T-G is described in ClinVar as [Benign]. Clinvar id is 1246297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1B	NM_001203.3	c.-17-257T>G		intron_variant		ENST00000515059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-17-257T>G		intron_variant		1	NM_001203.3	P4

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127076 AN: 151688 Hom.: 53225 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.817

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.838 AC: 127172 AN: 151806 Hom.: 53262 Cov.: 31 AF XY: 0.838 AC XY: 62146 AN XY: 74194

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.826

Alfa AF: 0.847 Hom.: 8824

Bravo AF: 0.837

Asia WGS AF: 0.831 AC: 2882 AN: 3470

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

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.3
Dann	Benign	0.49

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: rs7665167; hg19: chr4-96025302;