rs11818239

Variant names:

• chr10-86900031-G-A
• rs11818239
• NM_004329.3:c.435G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86900031-G-A
• chr10-86900031-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004329.3(BMPR1A):​c.435G>A​(p.Pro145Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00762 in 1,614,050 control chromosomes in the GnomAD database, including 798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P145P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.040 (412 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (386 hom.)
• Consequence: BMPR1A NM_004329.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:22
• Conservation: PhyloP100: -0.888
• Publications: 9 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: Genomics England PanelApp, Orphanet, Ambry Genetics
• juvenile polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 10-86900031-G-A is Benign according to our data. Variant chr10-86900031-G-A is described in ClinVar as Benign. ClinVar VariationId is 183708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.888 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	NM_004329.3	MANE Select	c.435G>A	p.Pro145Pro	synonymous	Exon 7 of 13	NP_004320.2
	BMPR1A	NM_001406559.1		c.435G>A	p.Pro145Pro	synonymous	Exon 7 of 14	NP_001393488.1
	BMPR1A	NM_001406560.1		c.435G>A	p.Pro145Pro	synonymous	Exon 7 of 14	NP_001393489.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.435G>A	p.Pro145Pro	synonymous	Exon 7 of 13	ENSP00000361107.2	P36894
	BMPR1A	ENST00000926286.1		c.435G>A	p.Pro145Pro	synonymous	Exon 7 of 14	ENSP00000596345.1
	BMPR1A	ENST00000480152.3	TSL:3	c.435G>A	p.Pro145Pro	synonymous	Exon 8 of 14	ENSP00000483569.2	P36894

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 6001 AN: 152132 Hom.: 406 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0107 AC: 2680 AN: 251326 AF XY: 0.00788

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.00795

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00428 AC: 6259 AN: 1461800 Hom.: 386 Cov.: 32 AF XY: 0.00368 AC XY: 2677 AN XY: 727208

African (AFR) AF: 0.145 AC: 4854 AN: 33462

American (AMR) AF: 0.00912 AC: 408 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53386

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5766

European-Non Finnish (NFE) AF: 0.000263 AC: 292 AN: 1111992

Other (OTH) AF: 0.0103 AC: 619 AN: 60388

GnomAD4 genome AF: 0.0396 AC: 6032 AN: 152250 Hom.: 412 Cov.: 32 AF XY: 0.0375 AC XY: 2795 AN XY: 74460

African (AFR) AF: 0.137 AC: 5672 AN: 41530

American (AMR) AF: 0.0158 AC: 242 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68022

Other (OTH) AF: 0.0308 AC: 65 AN: 2110

Alfa AF: 0.0123 Hom.: 231

Bravo AF: 0.0456

Asia WGS AF: 0.00982 AC: 36 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	6	Hereditary cancer-predisposing syndrome (6)
-	-	3	Juvenile polyposis syndrome (3)
-	-	3	not provided (3)
-	-	1	Generalized juvenile polyposis/juvenile polyposis coli (1)
-	-	1	Polyposis syndrome, hereditary mixed, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.0
DANN	Benign	0.87
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11818239; hg19: chr10-88659788;