10-86756585-C-T

Position:

• chr10-86756585-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001406562.1(BMPR1A):​c.-373+481C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 150,292 control chromosomes in the GnomAD database, including 7,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7547 hom., cov: 31)
  • Exomes 𝑓: 0.29 (2 hom.)
• Consequence: BMPR1A NM_001406562.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.21

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-86756585-C-T is Benign according to our data. Variant chr10-86756585-C-T is described in ClinVar as [Benign]. Clinvar id is 1264362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86756585-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.-602C>T		upstream_gene_variant		ENST00000372037.8	NP_004320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-602C>T		upstream_gene_variant		1	NM_004329.3	ENSP00000361107.2
BMPR1A	ENST00000635816.2	n.-602C>T		upstream_gene_variant		5		ENSP00000489707.1
BMPR1A	ENST00000636056.2	n.-602C>T		upstream_gene_variant		5		ENSP00000490273.1
BMPR1A	ENST00000638429.1	n.-602C>T		upstream_gene_variant		5		ENSP00000492290.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43338 AN: 150128 Hom.: 7548 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.293 AC: 17 AN: 58 Hom.: 2 Cov.: 0 AF XY: 0.313 AC XY: 15 AN XY: 48

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.288 AC: 43339 AN: 150234 Hom.: 7547 Cov.: 31 AF XY: 0.295 AC XY: 21675 AN XY: 73390

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.293

Alfa AF: 0.308 Hom.: 968

Bravo AF: 0.278

Asia WGS AF: 0.422 AC: 1409 AN: 3338

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 19, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61858562; hg19: chr10-88516342;