rs7070369

Variant names:

• chr10-86756209-G-A
• rs7070369
• ENST00000608826.2:n.178C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-86756209-G-A
• chr10-86756209-G-C
• chr10-86756209-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000608826.2(ENSG00000272631):​n.178C>T 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 0.289 in 151,980 control chromosomes in the GnomAD database, including 7,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7630 hom., cov: 32)
  • Exomes 𝑓: 0.70 (7 hom.)
• Consequence: ENSG00000272631 ENST00000608826.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0600
• Publications: 3 publications found

Genes affected

ENSG00000272631 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-86756209-G-A is Benign according to our data. Variant chr10-86756209-G-A is described in ClinVar as Benign. ClinVar VariationId is 1229698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_001406562.1	c.-373+105G>A		intron_variant	Intron 1 of 13		NP_001393491.1
BMPR1A	NM_001406564.1	c.-373+246G>A		intron_variant	Intron 1 of 13		NP_001393493.1
BMPR1A	NM_001406566.1	c.-268+246G>A		intron_variant	Intron 1 of 12		NP_001393495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272631	ENST00000608826.2	n.178C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000272631	ENST00000740897.1	n.68C>T		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000272631	ENST00000740898.1	n.62C>T		non_coding_transcript_exon_variant	Exon 1 of 2
BMPR1A	ENST00000713669.1	c.-268+107G>A		intron_variant	Intron 1 of 12			ENSP00000518971.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43948 AN: 151834 Hom.: 7629 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.700 AC: 21 AN: 30 Hom.: 7 Cov.: 0 AF XY: 0.750 AC XY: 15 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.708 AC: 17 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.289 AC: 43955 AN: 151950 Hom.: 7630 Cov.: 32 AF XY: 0.296 AC XY: 21997 AN XY: 74286

African (AFR) AF: 0.123 AC: 5110 AN: 41532

American (AMR) AF: 0.324 AC: 4953 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1374 AN: 3462

East Asian (EAS) AF: 0.695 AC: 3551 AN: 5112

South Asian (SAS) AF: 0.353 AC: 1697 AN: 4810

European-Finnish (FIN) AF: 0.391 AC: 4124 AN: 10548

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.328 AC: 22288 AN: 67894

Other (OTH) AF: 0.292 AC: 616 AN: 2112

Alfa AF: 0.313 Hom.: 1376

Bravo AF: 0.278

Asia WGS AF: 0.433 AC: 1502 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.4
DANN	Benign	0.84
PhyloP100		-0.060
PromoterAI		-0.015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7070369; hg19: chr10-88515966;