14-53949883-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001202.6(BMP4):c.*148_*149insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (1 hom.)
• Consequence: BMP4 NM_001202.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 14-53949883-C-CTT is Benign according to our data. Variant chr14-53949883-C-CTT is described in ClinVar as [Benign]. Clinvar id is 2644247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00108 (145/134396) while in subpopulation AFR AF= 0.0033 (111/33672). AF 95% confidence interval is 0.0028. There are 0 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP4	NM_001202.6	c.*148_*149insAA		3_prime_UTR_variant	4/4	ENST00000245451.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP4	ENST00000245451.9	c.*148_*149insAA		3_prime_UTR_variant	4/4	1	NM_001202.6	P1
BMP4	ENST00000558984.1	c.*148_*149insAA		3_prime_UTR_variant	3/3	1		P1
BMP4	ENST00000559087.5	c.*148_*149insAA		3_prime_UTR_variant	4/4	1		P1
BMP4	ENST00000417573.5	c.*148_*149insAA		3_prime_UTR_variant	4/4	5		P1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 144 AN: 134402 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00211

GnomAD4 exome AF: 0.00287 AC: 1460 AN: 508366 Hom.: 1 Cov.: 0 AF XY: 0.00274 AC XY: 705 AN XY: 257092

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.00449

Gnomad4 ASJ exome AF: 0.00422

Gnomad4 EAS exome AF: 0.000625

Gnomad4 SAS exome AF: 0.00140

Gnomad4 FIN exome AF: 0.00279

Gnomad4 NFE exome AF: 0.00216

Gnomad4 OTH exome AF: 0.00391

GnomAD4 genome AF: 0.00108 AC: 145 AN: 134396 Hom.: 0 Cov.: 0 AF XY: 0.00105 AC XY: 68 AN XY: 64696

Gnomad4 AFR AF: 0.00330

Gnomad4 AMR AF: 0.000380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00211

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

BMP4: BS1, BS2 -

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;