10-86851365-T-C

Variant names:

• chr10-86851365-T-C
• rs2883420
• NM_004329.3:c.-153+12386T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001406579.1(BMPR1A):​c.-552-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,070 control chromosomes in the GnomAD database, including 22,679 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22679 hom., cov: 33)
• Consequence: BMPR1A NM_001406579.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.-153+12386T>C		intron_variant	Intron 2 of 12	ENST00000372037.8	NP_004320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-153+12386T>C		intron_variant	Intron 2 of 12	1	NM_004329.3	ENSP00000361107.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78861 AN: 151952 Hom.: 22622 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.519 AC: 78967 AN: 152070 Hom.: 22679 Cov.: 33 AF XY: 0.524 AC XY: 38970 AN XY: 74320

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.488

Alfa AF: 0.425 Hom.: 6776

Bravo AF: 0.527

Asia WGS AF: 0.607 AC: 2112 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	0.60
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs2883420; hg19: chr10-88611122;