rs7698964

Positions:

• chr4-94935823-G-A

Variant summary

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

The ENST00000515059.6(BMPR1B):​c.-113+59923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 151,976 control chromosomes in the GnomAD database, including 2,773 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 0.17 (2773 hom., cov: 33)
• Consequence: BMPR1B ENST00000515059.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.-113+59923G>A		intron_variant		ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-113+59923G>A		intron_variant		1	NM_001203.3	ENSP00000426617	P4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25287 AN: 151858 Hom.: 2772 Cov.: 33

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.167 AC: 25324 AN: 151976 Hom.: 2773 Cov.: 33 AF XY: 0.166 AC XY: 12301 AN XY: 74302

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.148

Alfa AF: 0.147 Hom.: 258

Bravo AF: 0.173

Asia WGS AF: 0.125 AC: 433 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.86
DANN	Benign	0.66

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: rs7698964; hg19: chr4-95856974;