Variant chr8-22165454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006129.5(BMP1):c.49C>T(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BMP1
NM_006129.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.293

Variant links:

Genes affected

BMP1 (HGNC:1067): (bone morphogenetic protein 1) This gene encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-beta superfamily, this gene encodes a protein that is not closely related to other known growth factors. This gene is expressed as alternatively spliced variants that share an N-terminal protease domain but differ in their C-terminal region. [provided by RefSeq, Aug 2008]

BMP1 links:

BMP1 (HGNC:):

BMP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.110814184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP1	NM_006129.5 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	1/20	ENST00000306385.10	NP_006120.1	P13497-1
BMP1	NM_001199.4 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	1/16	ENST00000306349.13	NP_001190.1	P13497-2
BMP1	NR_033403.2 linkuse as main transcript	n.83C>T		non_coding_transcript_exon_variant	1/20
BMP1	NR_033404.2 linkuse as main transcript	n.83C>T		non_coding_transcript_exon_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	1/20	1	NM_006129.5	ENSP00000305714.5		P13497-1
BMP1	ENST00000306349.13 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	1/16	1	NM_001199.4	ENSP00000306121.8		P13497-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710410

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Osteogenesis imperfecta

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.089

T;T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;.;.;L

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.91

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.55

T;T;T;T

Sift4G

Benign

0.43

T;T;T;T

Polyphen

0.0010

B;.;.;B

Vest4

0.15

MutPred

0.20

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.53

MPC

0.40

ClinPred

0.050

GERP RS

-2.0

Varity_R

0.044

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over