rs2761880

Variant names:

• chr14-53952268-T-C
• rs2761880
• NM_001202.6:c.-7-39A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-53952268-T-C
• chr14-53952268-T-G

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.673
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• microphthalmia with brain and digit anomalies

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Stickler syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• orofacial cleft 11

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1192498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.-7-39A>G		intron_variant	Intron 2 of 3	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.-7-39A>G		intron_variant	Intron 2 of 3	1	NM_001202.6	ENSP00000245451.4

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

GnomAD2 exomes AF: 0.887 AC: 215725 AN: 243256 AF XY: 0.894

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 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

African (AFR) AF: 0.555 AC: 18450 AN: 33226

American (AMR) AF: 0.798 AC: 35411 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.964 AC: 25079 AN: 26008

East Asian (EAS) AF: 0.760 AC: 30119 AN: 39642

South Asian (SAS) AF: 0.823 AC: 70374 AN: 85522

European-Finnish (FIN) AF: 0.991 AC: 50536 AN: 51010

Middle Eastern (MID) AF: 0.903 AC: 5184 AN: 5744

European-Non Finnish (NFE) AF: 0.981 AC: 1085488 AN: 1106260

Other (OTH) AF: 0.916 AC: 55087 AN: 60150

GnomAD4 genome AF: 0.836 AC: 127012 AN: 151964 Hom.: 55507 Cov.: 30 AF XY: 0.836 AC XY: 62100 AN XY: 74312

African (AFR) AF: 0.574 AC: 23729 AN: 41324

American (AMR) AF: 0.819 AC: 12516 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 3358 AN: 3472

East Asian (EAS) AF: 0.703 AC: 3599 AN: 5120

South Asian (SAS) AF: 0.808 AC: 3887 AN: 4812

European-Finnish (FIN) AF: 0.993 AC: 10546 AN: 10618

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.978 AC: 66489 AN: 68014

Other (OTH) AF: 0.857 AC: 1808 AN: 2110

Alfa AF: 0.926 Hom.: 48218

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microphthalmia with brain and digit anomalies Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		0.67
PromoterAI		0.067	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2761880; hg19: chr14-54418986;