Variant 14-53952268-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001202.6(BMP4):c.-7-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,603,892 control chromosomes in the GnomAD database, including 712,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 55507 hom., cov: 30)

Exomes 𝑓: 0.95 ( 657440 hom. )

Consequence

BMP4
NM_001202.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.673

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 14-53952268-T-C is Benign according to our data. Variant chr14-53952268-T-C is described in ClinVar as [Benign]. Clinvar id is 1192498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-53952268-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP4	NM_001202.6 linkuse as main transcript	c.-7-39A>G		intron_variant		ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9 linkuse as main transcript	c.-7-39A>G		intron_variant		1	NM_001202.6	ENSP00000245451	P1

Frequencies

GnomAD3 genomes

AF:

0.836

AC:

126945

AN:

151846

Hom.:

55483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.896

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.967

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.993

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.978

Gnomad OTH

AF:

0.858

GnomAD3 exomes

AF:

0.887

AC:

215725

AN:

243256

Hom.:

97545

AF XY:

0.894

AC XY:

118723

AN XY:

132758

show subpopulations

Gnomad AFR exome

AF:

0.571

Gnomad AMR exome

AF:

0.798

Gnomad ASJ exome

AF:

0.963

Gnomad EAS exome

AF:

0.713

Gnomad SAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.991

Gnomad NFE exome

AF:

0.977

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.948

AC:

1375728

AN:

1451928

Hom.:

657440

Cov.:

AF XY:

0.946

AC XY:

683594

AN XY:

722946

show subpopulations

Gnomad4 AFR exome

AF:

0.555

Gnomad4 AMR exome

AF:

0.798

Gnomad4 ASJ exome

AF:

0.964

Gnomad4 EAS exome

AF:

0.760

Gnomad4 SAS exome

AF:

0.823

Gnomad4 FIN exome

AF:

0.991

Gnomad4 NFE exome

AF:

0.981

Gnomad4 OTH exome

AF:

0.916

GnomAD4 genome

AF:

0.836

AC:

127012

AN:

151964

Hom.:

55507

Cov.:

AF XY:

0.836

AC XY:

62100

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.574

Gnomad4 AMR

AF:

0.819

Gnomad4 ASJ

AF:

0.967

Gnomad4 EAS

AF:

0.703

Gnomad4 SAS

AF:

0.808

Gnomad4 FIN

AF:

0.993

Gnomad4 NFE

AF:

0.978

Gnomad4 OTH

AF:

0.857

Alfa

AF:

0.921

Hom.:

23862

Bravo

AF:

0.811

Asia WGS

AF:

0.749

AC:

2604

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.33

CADD

Benign

DANN

Benign

0.85

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