14-53955199-G-C

Variant names:

• chr14-53955199-G-C
• rs2855530
• NM_001202.6:c.-133+1351C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001202.6(BMP4):​c.-133+1351C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,074 control chromosomes in the GnomAD database, including 18,809 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 0.50 (18809 hom., cov: 33)
• Consequence: BMP4 NM_001202.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 15 publications found

Genes affected

BMP4 (HGNC:1071): (bone morphogenetic protein 4) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]

BMP4 Gene-Disease associations (from GenCC):

• BMP4-related ocular growth disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• microphthalmia with brain and digit anomalies

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• Stickler syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• orofacial cleft 11

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LOC124903317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP4	NM_001202.6	MANE Select	c.-133+1351C>G		intron	N/A	NP_001193.2	P12644
	BMP4	NM_001347912.1		c.62+1560C>G		intron	N/A	NP_001334841.1
	BMP4	NM_130850.5		c.-133+1560C>G		intron	N/A	NP_570911.2	Q53XC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP4	ENST00000245451.9	TSL:1 MANE Select	c.-133+1351C>G		intron	N/A	ENSP00000245451.4	P12644
	BMP4	ENST00000559087.5	TSL:1	c.-133+1560C>G		intron	N/A	ENSP00000453485.1	P12644
	BMP4	ENST00000890807.1		c.-706C>G		5_prime_UTR	Exon 1 of 4	ENSP00000560866.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75347 AN: 151956 Hom.: 18809 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.496 AC: 75381 AN: 152074 Hom.: 18809 Cov.: 33 AF XY: 0.499 AC XY: 37087 AN XY: 74344

African (AFR) AF: 0.454 AC: 18862 AN: 41516

American (AMR) AF: 0.493 AC: 7543 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1890 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2398 AN: 5110

South Asian (SAS) AF: 0.477 AC: 2302 AN: 4822

European-Finnish (FIN) AF: 0.548 AC: 5808 AN: 10600

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34926 AN: 67946

Other (OTH) AF: 0.487 AC: 1026 AN: 2108

Alfa AF: 0.524 Hom.: 2644

Bravo AF: 0.485

Asia WGS AF: 0.498 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.62
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2855530; hg19: chr14-54421917;