chr8-22165428-C-A

Variant names:

• chr8-22165428-C-A
• rs778373466
• NM_006129.5:c.23C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006129.5(BMP1):​c.23C>A​(p.Pro8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMP1 NM_006129.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23132694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP1	NM_006129.5	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 20	ENST00000306385.10	NP_006120.1
BMP1	NM_001199.4	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 16	ENST00000306349.13	NP_001190.1
BMP1	NR_033403.2	n.57C>A		non_coding_transcript_exon_variant	Exon 1 of 20
BMP1	NR_033404.2	n.57C>A		non_coding_transcript_exon_variant	Exon 1 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 20	1	NM_006129.5	ENSP00000305714.5
BMP1	ENST00000306349.13	c.23C>A	p.Pro8Gln	missense_variant	Exon 1 of 16	1	NM_001199.4	ENSP00000306121.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1398456 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 694942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.080	T;T;.;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.7	L;.;.;L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.92	N;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.17	T;D;D;T
Sift4G	Benign	0.076	T;T;T;T
Polyphen		0.0030	B;.;.;B
Vest4		0.22
MutPred		0.32		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.48
MPC		0.37
ClinPred		0.30	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.43

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: rs778373466; hg19: chr8-22022941;