rs3924231

Positions:

• chr8-22192267-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006129.5(BMP1):​c.1180+116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 855,576 control chromosomes in the GnomAD database, including 20,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (7012 hom., cov: 33)
  • Exomes 𝑓: 0.18 (13806 hom.)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-22192267-A-G is Benign according to our data. Variant chr8-22192267-A-G is described in ClinVar as [Benign]. Clinvar id is 675112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP1	NM_001199.4	c.1180+116A>G		intron_variant		ENST00000306349.13
BMP1	NM_006129.5	c.1180+116A>G		intron_variant		ENST00000306385.10
BMP1	NR_033403.2	n.1251+116A>G		intron_variant, non_coding_transcript_variant
BMP1	NR_033404.2	n.1251+116A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP1	ENST00000306349.13	c.1180+116A>G		intron_variant		1	NM_001199.4
BMP1	ENST00000306385.10	c.1180+116A>G		intron_variant		1	NM_006129.5	P1
	ENST00000647689.1	n.260+52T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41350 AN: 151856 Hom.: 6991 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.184 AC: 129567 AN: 703602 Hom.: 13806 Cov.: 9 AF XY: 0.182 AC XY: 66029 AN XY: 363790

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.0944

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.273 AC: 41423 AN: 151974 Hom.: 7012 Cov.: 33 AF XY: 0.276 AC XY: 20534 AN XY: 74290

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.243

Alfa AF: 0.181 Hom.: 2619

Bravo AF: 0.275

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.66
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3924231; hg19: chr8-22049780;