rs2761887

Positions:

• chr14-53958334-C-A
• chr14-53958334-C-T

Variant summary

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

The XM_047432035.1(LOC124903317):​c.428+2006C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,074 control chromosomes in the GnomAD database, including 25,081 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 0.57 (25081 hom., cov: 33)
• Consequence: LOC124903317 XM_047432035.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124903317	XM_047432035.1	c.428+2006C>A		intron_variant			XP_047287991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000667337.1	n.1658+2006C>A		intron_variant, non_coding_transcript_variant
BMP4	ENST00000559642.1	c.-133+386G>T		intron_variant		3		ENSP00000453467

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87211 AN: 151956 Hom.: 25065 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.574 AC: 87263 AN: 152074 Hom.: 25081 Cov.: 33 AF XY: 0.576 AC XY: 42833 AN XY: 74322

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.582

Alfa AF: 0.569 Hom.: 40058

Bravo AF: 0.570

Asia WGS AF: 0.624 AC: 2172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2761887; hg19: chr14-54425052;