Genetic Variant BMPR1A:c.68-643G>A (chr10-86889419-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004329.3(BMPR1A):c.68-643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 152,378 control chromosomes in the GnomAD database, including 384 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 0.068 ( 384 hom., cov: 33)

Exomes 𝑓: 0.087 ( 0 hom. )

Consequence

BMPR1A
NM_004329.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460

Publications

9 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 links:

RNU1-19P (HGNC:41945): (RNA, U1 small nuclear 19, pseudogene)

RNU1-19P links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 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.68-643G>A	intron	N/A	NP_004320.2
BMPR1A	NM_001406559.1		c.68-643G>A	intron	N/A	NP_001393488.1
BMPR1A	NM_001406560.1		c.68-643G>A	intron	N/A	NP_001393489.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.68-643G>A	intron	N/A	ENSP00000361107.2
BMPR1A	ENST00000480152.3	TSL:3	c.68-643G>A	intron	N/A	ENSP00000483569.2
BMPR1A	ENST00000713672.1		c.68-643G>A	intron	N/A	ENSP00000518974.1

Frequencies

GnomAD3 genomes

AF:

0.0676

AC:

10280

AN:

152110

Hom.:

383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0469

Gnomad ASJ

AF:

0.0986

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0609

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0715

Gnomad OTH

AF:

0.0565

GnomAD4 exome

AF:

0.0867

AC:

AN:

150

Hom.:

AF XY:

0.0625

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0714

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0932

AC:

AN:

118

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0675

AC:

10278

AN:

152228

Hom.:

384

Cov.:

AF XY:

0.0675

AC XY:

5019

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0624

AC:

2593

AN:

41552

American (AMR)

AF:

0.0467

AC:

714

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0986

AC:

342

AN:

3470

East Asian (EAS)

AF:

0.0713

AC:

370

AN:

5188

South Asian (SAS)

AF:

0.115

AC:

554

AN:

4816

European-Finnish (FIN)

AF:

0.0609

AC:

645

AN:

10586

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0715

AC:

4861

AN:

68018

Other (OTH)

AF:

0.0554

AC:

117

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

496

993

1489

1986

2482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0718

Hom.:

737

Bravo

AF:

0.0639

Asia WGS

AF:

0.0860

AC:

300

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.8

(source)

DANN

Benign

0.47

PhyloP100

0.046

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

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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