rs13257482

Positions:

• chr8-22202093-G-A
• chr8-22202093-G-C

Variant summary

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

The NM_006129.5(BMP1):​c.2233+165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,152 control chromosomes in the GnomAD database, including 16,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.39 (16710 hom., cov: 33)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.10

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=-0.91).
• BP6: Variant 8-22202093-G-A is Benign according to our data. Variant chr8-22202093-G-A is described in ClinVar as [Benign]. Clinvar id is 680516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP1	NM_006129.5	c.2233+165G>A		intron_variant		ENST00000306385.10	NP_006120.1
BMP1	NR_033403.2	n.2304+165G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10	c.2233+165G>A		intron_variant		1	NM_006129.5	ENSP00000305714	P1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59561 AN: 152034 Hom.: 16657 Cov.: 33

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.392 AC: 59671 AN: 152152 Hom.: 16710 Cov.: 33 AF XY: 0.392 AC XY: 29122 AN XY: 74372

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.349

Alfa AF: 0.247 Hom.: 3223

Bravo AF: 0.410

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 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. -
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	-0.91
CADD	Benign	0.057
DANN	Benign	0.36

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: rs13257482; hg19: chr8-22059606;