Genetic Variant BMP1:p.Gly12Gly (chr8-22165441-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_006129.5(BMP1):c.36G>T(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000493 in 1,421,122 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

BMP1
NM_006129.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 8-22165441-G-T is Benign according to our data. Variant chr8-22165441-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3005374.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP1	NM_006129.5 link	c.36G>T	p.Gly12Gly	synonymous_variant	Exon 1 of 20	ENST00000306385.10	NP_006120.1	P13497-1
BMP1	NM_001199.4 link	c.36G>T	p.Gly12Gly	synonymous_variant	Exon 1 of 16	ENST00000306349.13	NP_001190.1	P13497-2
BMP1	NR_033403.2 link	n.70G>T		non_coding_transcript_exon_variant	Exon 1 of 20
BMP1	NR_033404.2 link	n.70G>T		non_coding_transcript_exon_variant	Exon 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10 link	c.36G>T	p.Gly12Gly	synonymous_variant	Exon 1 of 20	1	NM_006129.5	ENSP00000305714.5		P13497-1
BMP1	ENST00000306349.13 link	c.36G>T	p.Gly12Gly	synonymous_variant	Exon 1 of 16	1	NM_001199.4	ENSP00000306121.8		P13497-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000519

AC:

AN:

192750

AF XY:

0.00000919

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000493

AC:

AN:

1421122

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

29336

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

39248

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

24802

Gnomad4 EAS exome

AF:

0.0000291

AC:

AN:

34366

Gnomad4 SAS exome

AF:

0.0000122

AC:

AN:

81990

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

51122

Gnomad4 NFE exome

AF:

0.00000456

AC:

AN:

1096296

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

58390

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over