rs2761880

chr14-53952268-T-Cchr14-53952268-T-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.673

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 -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	UniProt
BMP4	NM_001202.6	c.-7-39A>G		intron_variant		ENST00000245451.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.836 AC: 126945 AN: 151846 Hom.: 55483 Cov.: 30

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

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.: 34 AF XY: 0.946 AC XY: 683594 AN XY: 722946

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.: 30 AF XY: 0.836 AC XY: 62100 AN XY: 74312

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Microphthalmia with brain and digit anomalies Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	17
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

Other links and lift over

dbSNP: rs2761880; hg19: chr14-54418986;