14-53949883-CTTTTTTTTTTT-CTTTTTTT

Variant names:

• chr14-53949883-CTTTT-C
• rs1555339771
• NM_001202.6:c.*145_*148delAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001202.6(BMP4):​c.*145_*148delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 644,156 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 0.0000074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000071 (0 hom.)
• Consequence: BMP4 NM_001202.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 36 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.*145_*148delAAAA		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.*145_*148delAAAA		3_prime_UTR_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000558984	c.*145_*148delAAAA		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000454134.1
BMP4	ENST00000559087	c.*145_*148delAAAA		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453485.1
BMP4	ENST00000417573	c.*145_*148delAAAA		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000394165.1

Frequencies

GnomAD3 genomes AF: 0.00000744 AC: 1 AN: 134408 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000706 AC: 36 AN: 509748 Hom.: 0 AF XY: 0.0000737 AC XY: 19 AN XY: 257758

Gnomad4 AFR exome AF: 0.0000806

Gnomad4 AMR exome AF: 0.0000667

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.0000403

Gnomad4 NFE exome AF: 0.0000641

Gnomad4 OTH exome AF: 0.0000763

GnomAD4 genome AF: 0.00000744 AC: 1 AN: 134408 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 64668

Gnomad4 AFR AF: 0.0000297

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

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;