14-53954901-C-T

Variant names:

• chr14-53954901-C-T
• rs76953585
• NM_001202.6:c.-132-1501G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001347916.1(BMP4):​c.-408G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 152,294 control chromosomes in the GnomAD database, including 491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.054 (491 hom., cov: 32)
• Consequence: BMP4 NM_001347916.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

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]

LOC124903317 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.-132-1501G>A		intron_variant	Intron 1 of 3	ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.-132-1501G>A		intron_variant	Intron 1 of 3	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000559087.5	c.-132-1501G>A		intron_variant	Intron 1 of 3	1		ENSP00000453485.1
BMP4	ENST00000559642.1	c.-132-1501G>A		intron_variant	Intron 1 of 2	3		ENSP00000453467.1
ENSG00000287156	ENST00000667337.1	n.231C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8280 AN: 152176 Hom.: 492 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.00989

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0545 AC: 8293 AN: 152294 Hom.: 491 Cov.: 32 AF XY: 0.0546 AC XY: 4067 AN XY: 74470

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00989

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0120 Hom.: 8

Bravo AF: 0.0588

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.8
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs76953585; hg19: chr14-54421619;