Variant rs2071047 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001202.6(BMP4):c.370+160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,171,306 control chromosomes in the GnomAD database, including 101,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12715 hom., cov: 32)

Exomes 𝑓: 0.41 ( 88530 hom. )

Consequence

BMP4
NM_001202.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0650

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-53951693-G-A is Benign according to our data. Variant chr14-53951693-G-A is described in ClinVar as [Benign]. Clinvar id is 1167991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 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.370+160C>T		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.370+160C>T		intron_variant		1	NM_001202.6	ENSP00000245451	P1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61868

AN:

151794

Hom.:

12709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.359

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.430

GnomAD4 exome

AF:

0.414

AC:

422296

AN:

1019394

Hom.:

88530

Cov.:

AF XY:

0.416

AC XY:

212478

AN XY:

511024

show subpopulations

Gnomad4 AFR exome

AF:

0.377

Gnomad4 AMR exome

AF:

0.449

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.467

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.421

GnomAD4 genome

AF:

0.408

AC:

61917

AN:

151912

Hom.:

12715

Cov.:

AF XY:

0.409

AC XY:

30391

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.411

Gnomad4 SAS

AF:

0.473

Gnomad4 FIN

AF:

0.359

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.430

Alfa

AF:

0.411

Hom.:

17452

Bravo

AF:

0.411

Asia WGS

AF:

0.452

AC:

1572

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	This variant is associated with the following publications: (PMID: 27379672) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Microphthalmia with brain and digit anomalies;C2677434:Orofacial cleft 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.6

DANN

Benign

0.71

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