Variant 8-22165422-G-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.17G>T(p.Arg6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

BMP1
NM_006129.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

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:

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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=0.21311086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BMP1	NM_006129.5 linkuse as main transcript	c.17G>T	p.Arg6Leu	missense_variant	1/20	ENST00000306385.10
BMP1	NM_001199.4 linkuse as main transcript	c.17G>T	p.Arg6Leu	missense_variant	1/16	ENST00000306349.13
BMP1	NR_033403.2 linkuse as main transcript	n.51G>T		non_coding_transcript_exon_variant	1/20
BMP1	NR_033404.2 linkuse as main transcript	n.51G>T		non_coding_transcript_exon_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP1	ENST00000306385.10 linkuse as main transcript	c.17G>T	p.Arg6Leu	missense_variant	1/20	1	NM_006129.5	P1	P13497-1
BMP1	ENST00000306349.13 linkuse as main transcript	c.17G>T	p.Arg6Leu	missense_variant	1/16	1	NM_001199.4		P13497-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388256

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689108

show subpopulations

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:

0.0000129

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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.17G>T (p.R6L) alteration is located in exon 1 (coding exon 1) of the BMP1 gene. This alteration results from a G to T substitution at nucleotide position 17, causing the arginine (R) at amino acid position 6 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;T;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;.;.;N

MutationTaster

Benign

0.97

N;N;N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.030

N;N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.028

D;D;D;D

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.21

MutPred

0.41

Loss of methylation at R6 (P = 0.0197);Loss of methylation at R6 (P = 0.0197);Loss of methylation at R6 (P = 0.0197);Loss of methylation at R6 (P = 0.0197);

MVP

0.55

MPC

0.49

ClinPred

0.71

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.32

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