Variant rs4075478 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006129.5(BMP1):c.1765+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,602,902 control chromosomes in the GnomAD database, including 127,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16955 hom., cov: 30)

Exomes 𝑓: 0.39 ( 110485 hom. )

Consequence

BMP1
NM_006129.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0340

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-22195610-T-C is Benign according to our data. Variant chr8-22195610-T-C is described in ClinVar as [Benign]. Clinvar id is 674968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
BMP1	NM_006129.5 linkuse as main transcript	c.1765+23T>C	intron_variant	ENST00000306385.10	NP_006120.1	P13497-1
BMP1	NM_001199.4 linkuse as main transcript	c.1765+23T>C	intron_variant	ENST00000306349.13	NP_001190.1	P13497-2
BMP1	NR_033403.2 linkuse as main transcript	n.1836+23T>C	intron_variant
BMP1	NR_033404.2 linkuse as main transcript	n.1836+23T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10 linkuse as main transcript	c.1765+23T>C		intron_variant		1	NM_006129.5	ENSP00000305714.5		P13497-1
BMP1	ENST00000306349.13 linkuse as main transcript	c.1765+23T>C		intron_variant		1	NM_001199.4	ENSP00000306121.8		P13497-2

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69595

AN:

151656

Hom.:

16918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.425

AC:

100276

AN:

236138

Hom.:

22354

AF XY:

0.414

AC XY:

53412

AN XY:

129164

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.542

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.545

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.385

AC:

558826

AN:

1451132

Hom.:

110485

Cov.:

AF XY:

0.384

AC XY:

277064

AN XY:

722008

show subpopulations

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.541

Gnomad4 ASJ exome

AF:

0.395

Gnomad4 EAS exome

AF:

0.567

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.459

AC:

69678

AN:

151770

Hom.:

16955

Cov.:

AF XY:

0.462

AC XY:

34235

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.616

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.391

Gnomad4 FIN

AF:

0.425

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.446

Alfa

AF:

0.384

Hom.:

14005

Bravo

AF:

0.472

Asia WGS

AF:

0.510

AC:

1775

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Osteogenesis imperfecta type 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.27

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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