8-22171155-C-T

Position:

• chr8-22171155-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006129.5(BMP1):​c.149-2447C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,114 control chromosomes in the GnomAD database, including 37,603 homozygotes. 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: 𝑓 0.70 (37599 hom., cov: 32)
  • Exomes 𝑓: 0.58 (4 hom.)
• Consequence: BMP1 NM_006129.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP1	NM_001199.4	c.149-2447C>T		intron_variant		ENST00000306349.13	NP_001190.1
BMP1	NM_006129.5	c.149-2447C>T		intron_variant		ENST00000306385.10	NP_006120.1
BMP1	NR_033403.2	n.183-2447C>T		intron_variant, non_coding_transcript_variant
BMP1	NR_033404.2	n.183-2447C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306349.13	c.149-2447C>T		intron_variant		1	NM_001199.4	ENSP00000306121
BMP1	ENST00000306385.10	c.149-2447C>T		intron_variant		1	NM_006129.5	ENSP00000305714	P1
	ENST00000619681.1	n.1818C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106655 AN: 151972 Hom.: 37559 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.583 AC: 14 AN: 24 Hom.: 4 Cov.: 0 AF XY: 0.550 AC XY: 11 AN XY: 20

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.702 AC: 106746 AN: 152090 Hom.: 37599 Cov.: 32 AF XY: 0.700 AC XY: 52036 AN XY: 74316

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.725

Alfa AF: 0.715 Hom.: 20411

Bravo AF: 0.709

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.42

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: rs4872360; hg19: chr8-22028668;