8-22165280-G-T

Variant names:

• chr8-22165280-G-T
• rs527604798
• ENST00000518913.5:n.-126G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000397814.7(BMP1):​c.-126G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 980,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: BMP1 ENST00000397814.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 13

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• high bone mass osteogenesis imperfecta

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• osteogenesis imperfecta type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397814.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	NM_006129.5	MANE Select	c.-126G>T		upstream_gene	N/A	NP_006120.1	P13497-1
	BMP1	NM_001199.4	MANE Plus Clinical	c.-126G>T		upstream_gene	N/A	NP_001190.1	P13497-2
	BMP1	NR_033403.2		n.-92G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP1	ENST00000518913.5	TSL:1	n.-126G>T		non_coding_transcript_exon	Exon 1 of 16	ENSP00000427950.1	B7ZKR5
	BMP1	ENST00000520970.5	TSL:1	n.-126G>T		non_coding_transcript_exon	Exon 1 of 19	ENSP00000428332.1	P13497-2
	BMP1	ENST00000518913.5	TSL:1	n.-126G>T		5_prime_UTR	Exon 1 of 16	ENSP00000427950.1	B7ZKR5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 980578 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 480322

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18962

American (AMR) AF: 0.00 AC: 0 AN: 8288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14690

East Asian (EAS) AF: 0.00 AC: 0 AN: 25418

South Asian (SAS) AF: 0.00 AC: 0 AN: 42968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2926

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 795052

Other (OTH) AF: 0.00 AC: 0 AN: 41884

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		1.0
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1

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

Other links and lift over

dbSNP: rs527604798; hg19: chr8-22022793;