Variant rs2855532 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001202.6(BMP4):c.-8+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 396,242 control chromosomes in the GnomAD database, including 36,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 12845 hom., cov: 31)

Exomes 𝑓: 0.43 ( 23211 hom. )

Consequence

BMP4
NM_001202.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.87

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 14-53953247-G-A is Benign according to our data. Variant chr14-53953247-G-A is described in ClinVar as [Benign]. Clinvar id is 1192499.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP4	NM_001202.6 linkuse as main transcript	c.-8+29C>T		intron_variant		ENST00000245451.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP4	ENST00000245451.9 linkuse as main transcript	c.-8+29C>T		intron_variant		1	NM_001202.6	P1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61562

AN:

151776

Hom.:

12842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.469

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.434

AC:

106107

AN:

244348

Hom.:

23211

Cov.:

AF XY:

0.434

AC XY:

53791

AN XY:

123966

show subpopulations

Gnomad4 AFR exome

AF:

0.306

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.375

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.459

Gnomad4 FIN exome

AF:

0.452

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.436

GnomAD4 genome

AF:

0.406

AC:

61606

AN:

151894

Hom.:

12845

Cov.:

AF XY:

0.406

AC XY:

30110

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.433

Hom.:

5346

Bravo

AF:

0.405

Asia WGS

AF:

0.446

AC:

1549

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microphthalmia with brain and digit anomalies

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over