14-53949883-C-CATTT

Variant names:

• chr14-53949883-C-CATTT
• rs796563569
• NM_001202.6:c.*148_*149insAAAT

Variant summary

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

The NM_001202.6(BMP4):​c.*148_*149insAAAT 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 0.0018 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (26 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 eas. gnomad4 allele frequency = 0.00176 (236/134404) while in subpopulation EAS AF= 0.0319 (144/4518). AF 95% confidence interval is 0.0276. There are 4 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 236 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 237 AN: 134410 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.00141

Gnomad FIN AF: 0.00129

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000926

Gnomad OTH AF: 0.00106

GnomAD4 exome AF: 0.00359 AC: 1826 AN: 508858 Hom.: 26 Cov.: 0 AF XY: 0.00370 AC XY: 953 AN XY: 257300

Gnomad4 AFR exome AF: 0.00363

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.00315

Gnomad4 EAS exome AF: 0.0120

Gnomad4 SAS exome AF: 0.00566

Gnomad4 FIN exome AF: 0.00190

Gnomad4 NFE exome AF: 0.00288

Gnomad4 OTH exome AF: 0.00462

GnomAD4 genome AF: 0.00176 AC: 236 AN: 134404 Hom.: 4 Cov.: 0 AF XY: 0.00178 AC XY: 115 AN XY: 64696

Gnomad4 AFR AF: 0.00196

Gnomad4 AMR AF: 0.000152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0319

Gnomad4 SAS AF: 0.00142

Gnomad4 FIN AF: 0.00129

Gnomad4 NFE AF: 0.0000927

Gnomad4 OTH AF: 0.00105

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;