8-22165142-CGGAG-C

Position:

• chr8-22165142-CGGAG-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The ENST00000354870.5(BMP1):​c.-247_-244del 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 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.668

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]

ACMG classification

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: {Uncertain_significance=1, Benign=1}.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP1	ENST00000354870.5	c.-247_-244del		5_prime_UTR_variant	1/21	5
BMP1	ENST00000397814.7	c.-247_-244del		5_prime_UTR_variant	1/5	4
BMP1	ENST00000520970.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 20974 AN: 121450 Hom.: 1975 Cov.: 25

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

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.: 25 AF XY: 0.179 AC XY: 10522 AN XY: 58706

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:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Osteogenesis Imperfecta, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs750344454; hg19: chr8-22022655;