14-53949884-T-C

Position:

• chr14-53949884-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1 BS2_Supporting

The NM_001202.6(BMP4):​c.*148A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 0)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: BMP4 NM_001202.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.04

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000114 (11/96724) while in subpopulation NFE AF= 0.000132 (10/75850). AF 95% confidence interval is 0.0000715. There are 0 homozygotes in gnomad4_exome. There are 4 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 11 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP4	NM_001202.6	c.*148A>G		3_prime_UTR_variant	4/4	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.*148A>G		3_prime_UTR_variant	4/4	1	NM_001202.6	ENSP00000245451	P1
BMP4	ENST00000558984.1	c.*148A>G		3_prime_UTR_variant	3/3	1		ENSP00000454134	P1
BMP4	ENST00000559087.5	c.*148A>G		3_prime_UTR_variant	4/4	1		ENSP00000453485	P1
BMP4	ENST00000417573.5	c.*148A>G		3_prime_UTR_variant	4/4	5		ENSP00000394165	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.000114 AC: 11 AN: 96724 Hom.: 0 Cov.: 0 AF XY: 0.0000832 AC XY: 4 AN XY: 48062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000476

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs76335800; hg19: chr14-54416602;