14-53952392-G-C

Variant names:

• chr14-53952392-G-C
• rs10130587
• NM_001202.6:c.-7-163C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001202.6(BMP4):​c.-7-163C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 147,082 control chromosomes in the GnomAD database, including 15,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.45 (15219 hom., cov: 27)
• Consequence: BMP4 NM_001202.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.42
• Publications: 20 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-53952392-G-C is Benign according to our data. Variant chr14-53952392-G-C is described in ClinVar as Benign. ClinVar VariationId is 1167993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP4	NM_001202.6	MANE Select	c.-7-163C>G		intron	N/A	NP_001193.2
	BMP4	NM_001347912.1		c.188-216C>G		intron	N/A	NP_001334841.1
	BMP4	NM_001347914.2		c.-7-163C>G		intron	N/A	NP_001334843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP4	ENST00000245451.9	TSL:1 MANE Select	c.-7-163C>G		intron	N/A	ENSP00000245451.4
	BMP4	ENST00000558984.1	TSL:1	c.-7-163C>G		intron	N/A	ENSP00000454134.1
	BMP4	ENST00000559087.5	TSL:1	c.-7-163C>G		intron	N/A	ENSP00000453485.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 66095 AN: 146980 Hom.: 15190 Cov.: 27

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.485

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.450 AC: 66166 AN: 147082 Hom.: 15219 Cov.: 27 AF XY: 0.448 AC XY: 32141 AN XY: 71712

African (AFR) AF: 0.526 AC: 21051 AN: 39988

American (AMR) AF: 0.518 AC: 7664 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1891 AN: 3410

East Asian (EAS) AF: 0.472 AC: 2280 AN: 4834

South Asian (SAS) AF: 0.478 AC: 2148 AN: 4494

European-Finnish (FIN) AF: 0.354 AC: 3511 AN: 9918

Middle Eastern (MID) AF: 0.524 AC: 151 AN: 288

European-Non Finnish (NFE) AF: 0.392 AC: 26059 AN: 66430

Other (OTH) AF: 0.488 AC: 989 AN: 2028

Alfa AF: 0.155 Hom.: 291

Bravo AF: 0.471

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.45
PhyloP100		1.4
PromoterAI		0.086	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: rs10130587; hg19: chr14-54419110;