Genetic Variant ENST00000354870:c.-247_-244delGGAG (chr8-22165142-CGGAG-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The ENST00000354870(BMP1):c.-247_-244delGGAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 333,266 control chromosomes in the GnomAD database, including 5,840 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.17 ( 1978 hom., cov: 25)

Exomes 𝑓: 0.19 ( 3862 hom. )

Consequence

BMP1
ENST00000354870 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.668

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 Benign. Variant got -9 ACMG points.

BP6

Variant 8-22165142-CGGAG-C is Benign according to our data. Variant chr8-22165142-CGGAG-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 362572.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
BMP1	NM_006129.5 link	c.-263_-260delGGAG	upstream_gene_variant	ENST00000306385.10	NP_006120.1	P13497-1
BMP1	NM_001199.4 link	c.-263_-260delGGAG	upstream_gene_variant	ENST00000306349.13	NP_001190.1	P13497-2
BMP1	NR_033403.2 link	n.-229_-226delGGAG	upstream_gene_variant
BMP1	NR_033404.2 link	n.-229_-226delGGAG	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10 link	c.-263_-260delGGAG		upstream_gene_variant		1	NM_006129.5	ENSP00000305714.5		P13497-1
BMP1	ENST00000306349.13 link	c.-263_-260delGGAG		upstream_gene_variant		1	NM_001199.4	ENSP00000306121.8		P13497-2

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

20974

AN:

121450

Hom.:

1975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0455

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.00587

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.173

GnomAD4 exome

AF:

0.192

AC:

40629

AN:

211722

Hom.:

3862

AF XY:

0.193

AC XY:

21014

AN XY:

109038

show subpopulations

Gnomad4 AFR exome

AF:

0.0570

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.00969

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.277

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.173

AC:

20987

AN:

121544

Hom.:

1978

Cov.:

AF XY:

0.179

AC XY:

10522

AN XY:

58706

show subpopulations

Gnomad4 AFR

AF:

0.0456

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.185

Gnomad4 EAS

AF:

0.00588

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.330

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.171

Asia WGS

AF:

0.0820

AC:

276

AN:

3368

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Osteogenesis Imperfecta, Recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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