10-86930027-G-C

Position:

• chr10-86930027-G-C

Variant summary

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

The ENST00000635816.2(BMPR1A):​c.*1650G>C variant causes a 3 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,240 control chromosomes in the GnomAD database, including 1,214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: BMPR1A ENST00000635816.2 3_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1A	NR_176213.1	n.3090-274G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000635816.2	c.*1650G>C		3_prime_UTR_variant, NMD_transcript_variant	14/14	5		ENSP00000489707
BMPR1A	ENST00000638429.1	c.*923-274G>C		intron_variant, NMD_transcript_variant		5		ENSP00000492290

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17696 AN: 152096 Hom.: 1213 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.115 AC: 3 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.0909 AC XY: 2 AN XY: 22

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.116 AC: 17703 AN: 152214 Hom.: 1214 Cov.: 32 AF XY: 0.115 AC XY: 8558 AN XY: 74410

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0660

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0996

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0488 Hom.: 37

Bravo AF: 0.115

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.31

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: rs7909264; hg19: chr10-88689784;