10-86851365-T-C

Variant names:

• chr10-86851365-T-C
• rs2883420
• NM_004329.3:c.-153+12386T>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.-153+12386T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,070 control chromosomes in the GnomAD database, including 22,679 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 0.52 (22679 hom., cov: 33)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 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.-153+12386T>C		intron	N/A	NP_004320.2
	BMPR1A	NM_001406559.1		c.-153+12386T>C		intron	N/A	NP_001393488.1
	BMPR1A	NM_001406560.1		c.-153+12386T>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.-153+12386T>C		intron	N/A	ENSP00000361107.2
	BMPR1A	ENST00000480152.3	TSL:3	c.-153+7855T>C		intron	N/A	ENSP00000483569.2
	BMPR1A	ENST00000713672.1		c.-152-24502T>C		intron	N/A	ENSP00000518974.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78861 AN: 151952 Hom.: 22622 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.519 AC: 78967 AN: 152070 Hom.: 22679 Cov.: 33 AF XY: 0.524 AC XY: 38970 AN XY: 74320

African (AFR) AF: 0.752 AC: 31185 AN: 41478

American (AMR) AF: 0.434 AC: 6624 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1821 AN: 3466

East Asian (EAS) AF: 0.782 AC: 4051 AN: 5182

South Asian (SAS) AF: 0.508 AC: 2448 AN: 4822

European-Finnish (FIN) AF: 0.510 AC: 5381 AN: 10546

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.382 AC: 25978 AN: 68002

Other (OTH) AF: 0.488 AC: 1028 AN: 2106

Alfa AF: 0.427 Hom.: 7684

Bravo AF: 0.527

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.74
PhyloP100		-2.3
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: rs2883420; hg19: chr10-88611122;