rs2071047

chr14-53951693-G-Achr14-53951693-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0650

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 -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	UniProt
BMP4	NM_001202.6	c.370+160C>T		intron_variant		ENST00000245451.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP4	ENST00000245451.9	c.370+160C>T		intron_variant		1	NM_001202.6	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61868 AN: 151794 Hom.: 12709 Cov.: 32

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.: 14 AF XY: 0.416 AC XY: 212478 AN XY: 511024

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.: 32 AF XY: 0.409 AC XY: 30391 AN XY: 74224

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

This variant is associated with the following publications: (PMID: 27379672) -

Microphthalmia with brain and digit anomalies;C2677434:Orofacial cleft 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs2071047; hg19: chr14-54418411; COSMIC: COSV55417383; COSMIC: COSV55417383;