chr10-86756413-T-G

Position:

• chr10-86756413-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001406562.1(BMPR1A):​c.-373+309T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 151,830 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMPR1A NM_001406562.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 10-86756413-T-G is Benign according to our data. Variant chr10-86756413-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1201703.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-86756413-T-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00824 (1251/151830) while in subpopulation NFE AF= 0.0134 (911/67842). AF 95% confidence interval is 0.0127. There are 6 homozygotes in gnomad4. There are 609 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1251 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1A	NM_001406562.1	c.-373+309T>G		intron_variant			NP_001393491.1
BMPR1A	NM_001406564.1	c.-373+450T>G		intron_variant			NP_001393493.1
BMPR1A	NM_001406566.1	c.-268+450T>G		intron_variant			NP_001393495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.00826 AC: 1253 AN: 151722 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00370

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00858

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.00574

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00824 AC: 1251 AN: 151830 Hom.: 6 Cov.: 32 AF XY: 0.00820 AC XY: 609 AN XY: 74246

Gnomad4 AFR AF: 0.00369

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.00858

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0122 Hom.: 2

Bravo AF: 0.00699

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.7
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs570332499; hg19: chr10-88516170;