ENST00000635816.2:n.*1650G>C

Variant names:

• chr10-86930027-G-C
• rs7909264
• ENST00000635816.2:n.*1650G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635816.2(BMPR1A):​n.*1650G>C variant causes a non coding transcript exon 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 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• Publications: 2 publications found

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]

BMPR1A Gene-Disease associations (from GenCC):

• generalized juvenile polyposis/juvenile polyposis coli

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Genomics England PanelApp
• juvenile polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• polyposis syndrome, hereditary mixed, 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• hereditary mixed polyposis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• pulmonary arterial hypertension

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BMPR1A	NR_176213.1	n.3090-274G>C		intron_variant	Intron 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000635816.2	n.*1650G>C		non_coding_transcript_exon_variant	Exon 14 of 14	5		ENSP00000489707.1
BMPR1A	ENST00000635816.2	n.*1650G>C		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000489707.1
BMPR1A	ENST00000638429.1	n.*923-274G>C		intron_variant	Intron 13 of 13	5		ENSP00000492290.1

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 2 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.176 AC: 7320 AN: 41524

American (AMR) AF: 0.0682 AC: 1043 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5182

South Asian (SAS) AF: 0.0660 AC: 318 AN: 4816

European-Finnish (FIN) AF: 0.142 AC: 1501 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0996 AC: 6775 AN: 68010

Other (OTH) AF: 0.109 AC: 230 AN: 2116

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
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7909264; hg19: chr10-88689784;