Genetic Variant BMP4:c.*148_*149insAAAAAT (chr14-53949883-C-CATTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001202.6(BMP4):c.*148_*149insAAAAAT 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 0.000030 ( 1 hom., cov: 0)

Exomes 𝑓: 0.000053 ( 3 hom. )

Consequence

BMP4
NM_001202.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.04

Variant links:

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]

BMP4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6 link	c.148_149insAAAAAT		3_prime_UTR_variant	Exon 4 of 4	ENST00000245451.9	NP_001193.2	P12644Q53XC5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BMP4	ENST00000245451 link	c.148_149insAAAAAT	3_prime_UTR_variant	Exon 4 of 4	1	NM_001202.6	ENSP00000245451.4	P12644
BMP4	ENST00000558984 link	c.148_149insAAAAAT	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000454134.1	P12644
BMP4	ENST00000559087 link	c.148_149insAAAAAT	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000453485.1	P12644
BMP4	ENST00000417573 link	c.148_149insAAAAAT	3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000394165.1	P12644

Frequencies

GnomAD3 genomes

AF:

0.0000298

AC:

AN:

134408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000463

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000530

AC:

AN:

509904

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

257846

show subpopulations

Gnomad4 AFR exome

AF:

0.000242

Gnomad4 AMR exome

AF:

0.0000666

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000680

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000502

Gnomad4 OTH exome

AF:

0.000114

GnomAD4 genome

AF:

0.0000298

AC:

AN:

134408

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

64668

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000118

Gnomad4 NFE

AF:

0.0000463

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over