10-86756311-G-T

Position:

• chr10-86756311-G-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+207G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 152,248 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: BMPR1A NM_001406562.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30

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=-0.67).
• BP6: Variant 10-86756311-G-T is Benign according to our data. Variant chr10-86756311-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1195222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86756311-G-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1A	NM_001406562.1	c.-373+207G>T		intron_variant			NP_001393491.1
BMPR1A	NM_001406564.1	c.-373+348G>T		intron_variant			NP_001393493.1
BMPR1A	NM_001406566.1	c.-268+348G>T		intron_variant			NP_001393495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272631	ENST00000608826.1	n.-13C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1742 AN: 152094 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0250 AC: 1 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0313 AC XY: 1 AN XY: 32

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0114 AC: 1737 AN: 152208 Hom.: 27 Cov.: 32 AF XY: 0.0125 AC XY: 933 AN XY: 74408

Gnomad4 AFR AF: 0.00241

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.0830

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.0114

Asia WGS AF: 0.0390 AC: 136 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.4
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11202163; hg19: chr10-88516068;