14-53956049-G-T

Position:

• chr14-53956049-G-T

Variant summary

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

The XM_047432035.1(LOC124903317):​c.149G>T​(p.Gly50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,512 control chromosomes in the GnomAD database, including 10,333 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (10300 hom., cov: 32)
  • Exomes 𝑓: 0.39 (33 hom.)
• Consequence: LOC124903317 XM_047432035.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

LOC124903317 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903317	XM_047432035.1	c.149G>T	p.Gly50Val	missense_variant	1/2		XP_047287991.1
BMP4	NM_001202.6	c.-133+501C>A		intron_variant		ENST00000245451.9	NP_001193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP4	ENST00000245451.9	c.-133+501C>A		intron_variant		1	NM_001202.6	ENSP00000245451	P1
	ENST00000667337.1	n.1379G>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52384 AN: 151972 Hom.: 10295 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.389 AC: 165 AN: 424 Hom.: 33 AF XY: 0.418 AC XY: 102 AN XY: 244

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.345 AC: 52406 AN: 152088 Hom.: 10300 Cov.: 32 AF XY: 0.345 AC XY: 25641 AN XY: 74326

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.360

Alfa AF: 0.397 Hom.: 2915

Bravo AF: 0.339

Asia WGS AF: 0.351 AC: 1221 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	0.28
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs762643; hg19: chr14-54422767;