rs4934275

Variant names:

• chr10-86857635-T-C
• rs4934275
• NM_004329.3:c.-152-18232T>C

Variant summary

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

The NM_004329.3(BMPR1A):​c.-152-18232T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,740 control chromosomes in the GnomAD database, including 2,670 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 0.15 (2670 hom., cov: 30)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 6 publications found

Genes affected

BMPR1A (HGNC:1076): (bone morphogenetic protein receptor type 1A) The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 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. [provided by RefSeq, Jul 2008]

BMPR1A Gene-Disease associations (from GenCC):

• generalized juvenile polyposis/juvenile polyposis coli

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Genomics England PanelApp
• juvenile polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• polyposis syndrome, hereditary mixed, 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• hereditary mixed polyposis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	NM_004329.3	MANE Select	c.-152-18232T>C		intron	N/A	NP_004320.2
	BMPR1A	NM_001406559.1		c.-152-18232T>C		intron	N/A	NP_001393488.1
	BMPR1A	NM_001406560.1		c.-152-18232T>C		intron	N/A	NP_001393489.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.-152-18232T>C		intron	N/A	ENSP00000361107.2
	BMPR1A	ENST00000480152.3	TSL:3	c.-153+14125T>C		intron	N/A	ENSP00000483569.2
	BMPR1A	ENST00000713672.1		c.-152-18232T>C		intron	N/A	ENSP00000518974.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22445 AN: 151620 Hom.: 2667 Cov.: 30

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.148 AC: 22448 AN: 151740 Hom.: 2670 Cov.: 30 AF XY: 0.155 AC XY: 11524 AN XY: 74132

African (AFR) AF: 0.0603 AC: 2500 AN: 41432

American (AMR) AF: 0.208 AC: 3163 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3406 AN: 5128

South Asian (SAS) AF: 0.156 AC: 749 AN: 4792

European-Finnish (FIN) AF: 0.215 AC: 2256 AN: 10472

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9030 AN: 67900

Other (OTH) AF: 0.161 AC: 340 AN: 2110

Alfa AF: 0.142 Hom.: 2495

Bravo AF: 0.150

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-1.6
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: rs4934275; hg19: chr10-88617392;