10-86923365-T-C

Variant names:

• chr10-86923365-T-C
• rs7074064
• NM_004329.3:c.1343-11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001406559.1(BMPR1A):​c.1418-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,613,372 control chromosomes in the GnomAD database, including 83,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (14930 hom., cov: 32)
  • Exomes 𝑓: 0.29 (68883 hom.)
• Consequence: BMPR1A NM_001406559.1 intron
• Scores: Splicing: ADA: 0.00009420
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.227
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-86923365-T-C is Benign according to our data. Variant chr10-86923365-T-C is described in ClinVar as Benign. ClinVar VariationId is 259286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001406559.1. 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.1343-11T>C		intron	N/A	NP_004320.2
	BMPR1A	NM_001406559.1		c.1418-11T>C		intron	N/A	NP_001393488.1
	BMPR1A	NM_001406560.1		c.1391-11T>C		intron	N/A	NP_001393489.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.1343-11T>C		intron	N/A	ENSP00000361107.2
	BMPR1A	ENST00000926286.1		c.1391-11T>C		intron	N/A	ENSP00000596345.1
	BMPR1A	ENST00000480152.3	TSL:3	c.1343-11T>C		intron	N/A	ENSP00000483569.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61046 AN: 151858 Hom.: 14879 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.386

GnomAD2 exomes AF: 0.354 AC: 89039 AN: 251350 AF XY: 0.340

Gnomad AFR exome AF: 0.671

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.718

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.288 AC: 421072 AN: 1461394 Hom.: 68883 Cov.: 34 AF XY: 0.287 AC XY: 208600 AN XY: 727018

African (AFR) AF: 0.684 AC: 22878 AN: 33462

American (AMR) AF: 0.362 AC: 16170 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9827 AN: 26126

East Asian (EAS) AF: 0.711 AC: 28230 AN: 39690

South Asian (SAS) AF: 0.304 AC: 26223 AN: 86246

European-Finnish (FIN) AF: 0.362 AC: 19356 AN: 53406

Middle Eastern (MID) AF: 0.367 AC: 2091 AN: 5690

European-Non Finnish (NFE) AF: 0.249 AC: 276750 AN: 1111690

Other (OTH) AF: 0.324 AC: 19547 AN: 60366

GnomAD4 genome AF: 0.402 AC: 61141 AN: 151978 Hom.: 14930 Cov.: 32 AF XY: 0.406 AC XY: 30175 AN XY: 74296

African (AFR) AF: 0.662 AC: 27433 AN: 41440

American (AMR) AF: 0.334 AC: 5101 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3464

East Asian (EAS) AF: 0.699 AC: 3596 AN: 5148

South Asian (SAS) AF: 0.315 AC: 1514 AN: 4808

European-Finnish (FIN) AF: 0.374 AC: 3955 AN: 10562

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17048 AN: 67950

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.303 Hom.: 34418

Bravo AF: 0.418

Asia WGS AF: 0.487 AC: 1694 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Juvenile polyposis syndrome (3)
-	-	3	not provided (3)
-	-	2	Generalized juvenile polyposis/juvenile polyposis coli (2)
-	-	2	Hereditary cancer-predisposing syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.32
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000094
dbscSNV1_RF	Benign	0.0040
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: rs7074064; hg19: chr10-88683122;