14-53955199-G-C

Position:

• chr14-53955199-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124903317 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP4	NM_001202.6	c.-133+1351C>G		intron_variant		ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.-133+1351C>G		intron_variant		1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000559087.5	c.-133+1560C>G		intron_variant		1		ENSP00000453485.1
BMP4	ENST00000559642.1	c.-132-1799C>G		intron_variant		3		ENSP00000453467.1
ENSG00000287156	ENST00000667337.1	n.529G>C		non_coding_transcript_exon_variant	1/2

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

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.487

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.62

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: rs2855530; hg19: chr14-54421917;