14-53949883-CTTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr14-53949883-C-CT
• rs1555339771
• NM_001202.6:c.*148dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001202.6(BMP4):​c.*148dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 0)
  • Exomes 𝑓: 0.011 (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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00257 (345/134400) while in subpopulation AFR AF= 0.00849 (286/33674). AF 95% confidence interval is 0.00768. There are 3 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 345 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.*148dupA		3_prime_UTR_variant	Exon 4 of 4	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451	c.*148dupA		3_prime_UTR_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000558984	c.*148dupA		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000454134.1
BMP4	ENST00000559087	c.*148dupA		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453485.1
BMP4	ENST00000417573	c.*148dupA		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000394165.1

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 346 AN: 134406 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00854

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00129

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00198

Gnomad SAS AF: 0.00112

Gnomad FIN AF: 0.000824

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00106

GnomAD4 exome AF: 0.0114 AC: 5803 AN: 509092 Hom.: 0 Cov.: 0 AF XY: 0.0112 AC XY: 2881 AN XY: 257432

Gnomad4 AFR exome AF: 0.0279

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.0100

Gnomad4 EAS exome AF: 0.0196

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.00609

Gnomad4 NFE exome AF: 0.00976

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.00257 AC: 345 AN: 134400 Hom.: 3 Cov.: 0 AF XY: 0.00261 AC XY: 169 AN XY: 64692

Gnomad4 AFR AF: 0.00849

Gnomad4 AMR AF: 0.00129

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00199

Gnomad4 SAS AF: 0.00113

Gnomad4 FIN AF: 0.000824

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00105

ClinVar

Not reported in ClinVar

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;