14-53949883-CTTTTTTTTTTT-CTTTTTT

Variant names:

• chr14-53949883-CTTTTT-C
• rs1555339771
• NM_001202.6:c.*144_*148delAAAAA

Variant summary

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

The NM_001202.6(BMP4):​c.*144_*148delAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 644,316 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00064 (4 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00035 (47/134410) while in subpopulation AMR AF= 0.000912 (12/13152). AF 95% confidence interval is 0.000526. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.*144_*148delAAAAA		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.*144_*148delAAAAA		3_prime_UTR_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000558984	c.*144_*148delAAAAA		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000454134.1
BMP4	ENST00000559087	c.*144_*148delAAAAA		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453485.1
BMP4	ENST00000417573	c.*144_*148delAAAAA		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000394165.1

Frequencies

GnomAD3 genomes AF: 0.000350 AC: 47 AN: 134410 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000912

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: 0.000479

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000641 AC: 327 AN: 509906 Hom.: 4 AF XY: 0.000632 AC XY: 163 AN XY: 257844

Gnomad4 AFR exome AF: 0.000242

Gnomad4 AMR exome AF: 0.000400

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000102

Gnomad4 FIN exome AF: 0.0000403

Gnomad4 NFE exome AF: 0.000828

Gnomad4 OTH exome AF: 0.000648

GnomAD4 genome AF: 0.000350 AC: 47 AN: 134410 Hom.: 0 Cov.: 0 AF XY: 0.000325 AC XY: 21 AN XY: 64670

Gnomad4 AFR AF: 0.000119

Gnomad4 AMR AF: 0.000912

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000479

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;