rs7895217

Variant names:

• chr10-86828982-T-A
• rs7895217
• NM_004329.3:c.-267-9883T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86828982-T-A
• chr10-86828982-T-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.-267-9883T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,884 control chromosomes in the GnomAD database, including 19,357 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 0.48 (19357 hom., cov: 31)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 10 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 (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.-267-9883T>A		intron_variant	Intron 1 of 12	ENST00000372037.8	NP_004320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-267-9883T>A		intron_variant	Intron 1 of 12	1	NM_004329.3	ENSP00000361107.2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72740 AN: 151766 Hom.: 19299 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.480 AC: 72849 AN: 151884 Hom.: 19357 Cov.: 31 AF XY: 0.485 AC XY: 35989 AN XY: 74242

African (AFR) AF: 0.698 AC: 28932 AN: 41424

American (AMR) AF: 0.419 AC: 6401 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1661 AN: 3464

East Asian (EAS) AF: 0.674 AC: 3466 AN: 5146

South Asian (SAS) AF: 0.405 AC: 1949 AN: 4808

European-Finnish (FIN) AF: 0.490 AC: 5164 AN: 10538

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23895 AN: 67928

Other (OTH) AF: 0.462 AC: 973 AN: 2108

Alfa AF: 0.407 Hom.: 1657

Bravo AF: 0.488

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		0.019
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: rs7895217; hg19: chr10-88588739;