8-22165391-C-G

Position:

chr8-22165391-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_006129.5(BMP1):c.-15C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,446,040 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 9 hom., cov: 33)

Exomes 𝑓: 0.012 ( 130 hom. )

Consequence

BMP1
NM_006129.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.397

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 8-22165391-C-G is Benign according to our data. Variant chr8-22165391-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 362575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00798 (1215/152268) while in subpopulation NFE AF= 0.0135 (919/67996). AF 95% confidence interval is 0.0128. There are 9 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
BMP1	NM_001199.4 linkuse as main transcript	c.-15C>G	5_prime_UTR_variant	1/16	ENST00000306349.13	NP_001190.1
BMP1	NM_006129.5 linkuse as main transcript	c.-15C>G	5_prime_UTR_variant	1/20	ENST00000306385.10	NP_006120.1
BMP1	NR_033403.2 linkuse as main transcript	n.20C>G	non_coding_transcript_exon_variant	1/20
BMP1	NR_033404.2 linkuse as main transcript	n.20C>G	non_coding_transcript_exon_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306349.13 linkuse as main transcript	c.-15C>G		5_prime_UTR_variant	1/16	1	NM_001199.4	ENSP00000306121		P13497-2
BMP1	ENST00000306385.10 linkuse as main transcript	c.-15C>G		5_prime_UTR_variant	1/20	1	NM_006129.5	ENSP00000305714	P1	P13497-1

Frequencies

GnomAD3 genomes

AF:

0.00800

AC:

1217

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00730

AC:

392

AN:

53690

Hom.:

AF XY:

0.00739

AC XY:

225

AN XY:

30442

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00534

Gnomad ASJ exome

AF:

0.00168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00351

Gnomad FIN exome

AF:

0.00468

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00613

GnomAD4 exome

AF:

0.0124

AC:

16024

AN:

1293772

Hom.:

130

Cov.:

AF XY:

0.0123

AC XY:

7808

AN XY:

635606

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00645

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0000687

Gnomad4 SAS exome

AF:

0.00425

Gnomad4 FIN exome

AF:

0.00445

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.00798

AC:

1215

AN:

152268

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00932

Hom.:

Bravo

AF:

0.00785

Asia WGS

AF:

0.000870

AC:

AN:

3462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 2017

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

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Interstitial lung disease 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pulmonary Surfactant Metabolism Dysfunction, Dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Osteogenesis Imperfecta, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.85

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