chr14-53949883-C-CATTTT

Variant names:

• chr14-53949883-C-CATTTT
• rs796563569
• NM_001202.6:c.*148_*149insAAAAT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1 BS2_Supporting

The NM_001202.6(BMP4):​c.*148_*149insAAAAT 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 0.000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (9 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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000316 (161/509786) while in subpopulation EAS AF= 0.00101 (29/28834). AF 95% confidence interval is 0.000719. There are 9 homozygotes in gnomad4_exome. There are 84 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.*148_*149insAAAAT		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.*148_*149insAAAAT		3_prime_UTR_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000558984	c.*148_*149insAAAAT		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000454134.1
BMP4	ENST00000559087	c.*148_*149insAAAAT		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453485.1
BMP4	ENST00000417573	c.*148_*149insAAAAT		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000394165.1

Frequencies

GnomAD3 genomes AF: 0.0000670 AC: 9 AN: 134410 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000119

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: 0.000353

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000309

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000316 AC: 161 AN: 509786 Hom.: 9 Cov.: 0 AF XY: 0.000326 AC XY: 84 AN XY: 257784

Gnomad4 AFR exome AF: 0.000403

Gnomad4 AMR exome AF: 0.0000667

Gnomad4 ASJ exome AF: 0.000726

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.000272

Gnomad4 FIN exome AF: 0.000202

Gnomad4 NFE exome AF: 0.000259

Gnomad4 OTH exome AF: 0.000420

GnomAD4 genome AF: 0.0000670 AC: 9 AN: 134404 Hom.: 0 Cov.: 0 AF XY: 0.0000155 AC XY: 1 AN XY: 64696

Gnomad4 AFR AF: 0.000119

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000353

Gnomad4 NFE AF: 0.0000309

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00269 Hom.: 747

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: rs796563569; hg19: chr14-54416601;