chr14-53949883-CT-C

Position:

• chr14-53949883-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001202.6(BMP4):​c.*148del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 0)
  • Exomes 𝑓: 0.10 (5 hom.)
• Consequence: BMP4 NM_001202.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 14-53949883-CT-C is Benign according to our data. Variant chr14-53949883-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189262.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1454 AN: 134336 Hom.: 10 Cov.: 0

Gnomad AFR AF: 0.00318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0327

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.00338

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00847

GnomAD4 exome AF: 0.101 AC: 50353 AN: 500220 Hom.: 5 Cov.: 0 AF XY: 0.101 AC XY: 25526 AN XY: 252876

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0864

Gnomad4 NFE exome AF: 0.0852

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0108 AC: 1454 AN: 134332 Hom.: 10 Cov.: 0 AF XY: 0.0113 AC XY: 732 AN XY: 64656

Gnomad4 AFR AF: 0.00318

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.0327

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.00340

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.00845

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs1555339771; hg19: chr14-54416601;