10-86912396-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004329.3(BMPR1A):c.675+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,613,626 control chromosomes in the GnomAD database, including 759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 389 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 370 hom. )

Consequence

BMPR1A
NM_004329.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -1.55

Publications

2 publications found

Variant links:

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

BMPR1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-86912396-G-A is Benign according to our data. Variant chr10-86912396-G-A is described in ClinVar as Benign. ClinVar VariationId is 259287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BMPR1A	NM_004329.3	MANE Select	c.675+12G>A	intron	N/A	NP_004320.2
BMPR1A	NM_001406559.1		c.750+12G>A	intron	N/A	NP_001393488.1
BMPR1A	NM_001406560.1		c.723+12G>A	intron	N/A	NP_001393489.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.675+12G>A	intron	N/A	ENSP00000361107.2	P36894
BMPR1A	ENST00000926286.1		c.723+12G>A	intron	N/A	ENSP00000596345.1
BMPR1A	ENST00000480152.3	TSL:3	c.675+12G>A	intron	N/A	ENSP00000483569.2	P36894

Frequencies

GnomAD3 genomes

AF:

0.0384

AC:

5841

AN:

152020

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0104

AC:

2625

AN:

251248

AF XY:

0.00774

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.00772

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00424

AC:

6203

AN:

1461488

Hom.:

370

Cov.:

AF XY:

0.00365

AC XY:

2657

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.142

AC:

4752

AN:

33452

American (AMR)

AF:

0.00879

AC:

393

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.000348

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00989

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000326

AC:

362

AN:

1111766

Other (OTH)

AF:

0.0101

AC:

608

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

268

536

804

1072

1340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0386

AC:

5868

AN:

152138

Hom.:

389

Cov.:

AF XY:

0.0365

AC XY:

2717

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.133

AC:

5511

AN:

41464

American (AMR)

AF:

0.0158

AC:

242

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68016

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

254

508

763

1017

1271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0180

Hom.:

147

Bravo

AF:

0.0444

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Hereditary cancer-predisposing syndrome (2)

Juvenile polyposis syndrome (2)

not provided (2)

Generalized juvenile polyposis/juvenile polyposis coli (1)

Polyposis syndrome, hereditary mixed, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.53

(source)

DANN

Benign

0.51

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over