14-53952392-G-C

Position:

• chr14-53952392-G-C

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.-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

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=-0.92).
• BP6: Variant 14-53952392-G-C is Benign according to our data. Variant chr14-53952392-G-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP4	NM_001202.6	c.-7-163C>G		intron_variant		ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.-7-163C>G		intron_variant		1	NM_001202.6	ENSP00000245451.4

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

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.488

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

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

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.45

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: rs10130587; hg19: chr14-54419110;