14-53949883-CTTTTTTTTTTT-CTTTTTTTTT

Variant names:

• chr14-53949883-CTT-C
• rs1555339771
• NM_001202.6:c.*147_*148delAA

Variant summary

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

The NM_001202.6(BMP4):​c.*147_*148delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 636,794 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.017 (0 hom.)
• Consequence: BMP4 NM_001202.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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 eas. gnomad4_exome allele frequency = 0.017 (8548/502428) while in subpopulation EAS AF= 0.0353 (975/27624). AF 95% confidence interval is 0.0335. There are 0 homozygotes in gnomad4_exome. There are 4358 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.*147_*148delAA		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.*147_*148delAA		3_prime_UTR_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000558984	c.*147_*148delAA		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000454134.1
BMP4	ENST00000559087	c.*147_*148delAA		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453485.1
BMP4	ENST00000417573	c.*147_*148delAA		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000394165.1

Frequencies

GnomAD3 genomes AF: 0.000134 AC: 18 AN: 134372 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000304

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0170 AC: 8548 AN: 502428 Hom.: 0 AF XY: 0.0172 AC XY: 4358 AN XY: 253970

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.0353

Gnomad4 SAS exome AF: 0.0244

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.000134 AC: 18 AN: 134366 Hom.: 0 Cov.: 0 AF XY: 0.000155 AC XY: 10 AN XY: 64668

Gnomad4 AFR AF: 0.0000594

Gnomad4 AMR AF: 0.000304

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000235

Gnomad4 NFE AF: 0.000154

Gnomad4 OTH AF: 0.00

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;