rs2761884

Variant names:

• chr14-53954334-G-T
• rs2761884
• NM_001202.6:c.-132-934C>A

Variant summary

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

The NM_001202.6(BMP4):​c.-132-934C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,798 control chromosomes in the GnomAD database, including 10,373 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 0.35 (10373 hom., cov: 30)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: BMP4 NM_001202.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP4	NM_001202.6	c.-132-934C>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.-132-934C>A		intron_variant	Intron 1 of 3	1	NM_001202.6	ENSP00000245451.4
BMP4	ENST00000559087.5	c.-132-934C>A		intron_variant	Intron 1 of 3	1		ENSP00000453485.1
BMP4	ENST00000417573.5	c.-133+87C>A		intron_variant	Intron 1 of 3	5		ENSP00000394165.1
BMP4	ENST00000559642.1	c.-132-934C>A		intron_variant	Intron 1 of 2	3		ENSP00000453467.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52542 AN: 151642 Hom.: 10368 Cov.: 30

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.250 AC: 9 AN: 36 Hom.: 0 AF XY: 0.281 AC XY: 9 AN XY: 32

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.346 AC: 52569 AN: 151762 Hom.: 10373 Cov.: 30 AF XY: 0.347 AC XY: 25712 AN XY: 74112

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.361

Alfa AF: 0.401 Hom.: 3746

Bravo AF: 0.340

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.79

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: rs2761884; hg19: chr14-54421052;