8-22165236-A-G

Position:

• chr8-22165236-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000520970.5(BMP1):​c.-170A>G variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 752,056 control chromosomes in the GnomAD database, including 225,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47540 hom., cov: 33)
  • Exomes 𝑓: 0.77 (177719 hom.)
• Consequence: BMP1 ENST00000520970.5 5_prime_UTR, NMD_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.00100

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-22165236-A-G is Benign according to our data. Variant chr8-22165236-A-G is described in ClinVar as [Benign]. Clinvar id is 362573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 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	ENST00000520970.5	c.-170A>G		5_prime_UTR_variant, NMD_transcript_variant	1/19	1
BMP1	ENST00000354870.5	c.-170A>G		5_prime_UTR_variant	1/21	5
BMP1	ENST00000397814.7	c.-170A>G		5_prime_UTR_variant	1/5	4
BMP1	ENST00000518913.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119833 AN: 151838 Hom.: 47489 Cov.: 33

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.768 AC: 460874 AN: 600110 Hom.: 177719 Cov.: 8 AF XY: 0.765 AC XY: 230779 AN XY: 301542

Gnomad4 AFR exome AF: 0.858

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.831

Gnomad4 EAS exome AF: 0.678

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.748

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.774

GnomAD4 genome AF: 0.789 AC: 119933 AN: 151946 Hom.: 47540 Cov.: 33 AF XY: 0.785 AC XY: 58322 AN XY: 74254

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.796

Alfa AF: 0.775 Hom.: 5367

Bravo AF: 0.802

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

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 14, 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. -

Interstitial lung disease 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pulmonary Surfactant Metabolism Dysfunction, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Osteogenesis Imperfecta, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs111596355; hg19: chr8-22022749;