14-53949883-CTTTTTTTTTTT-CTTTTTTTTTTTTTTT

Variant names:

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

Variant summary

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

The NM_001202.6(BMP4):​c.*145_*148dupAAAA 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 0.00031 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00058 (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 = 0.000305 (41/134398) while in subpopulation AFR AF= 0.00095 (32/33668). AF 95% confidence interval is 0.000691. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000305 AC: 41 AN: 134404 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000952

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: 0.000118

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000618

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000579 AC: 295 AN: 509686 Hom.: 0 Cov.: 0 AF XY: 0.000516 AC XY: 133 AN XY: 257742

Gnomad4 AFR exome AF: 0.00694

Gnomad4 AMR exome AF: 0.000934

Gnomad4 ASJ exome AF: 0.000807

Gnomad4 EAS exome AF: 0.0000347

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.000403

Gnomad4 NFE exome AF: 0.000413

Gnomad4 OTH exome AF: 0.000725

GnomAD4 genome AF: 0.000305 AC: 41 AN: 134398 Hom.: 0 Cov.: 0 AF XY: 0.000263 AC XY: 17 AN XY: 64692

Gnomad4 AFR AF: 0.000950

Gnomad4 AMR AF: 0.000304

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000118

Gnomad4 NFE AF: 0.0000618

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;