rs77671695

chr14-53957320-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XM_047432035.1(LOC124903317):c.428+992T>G variant causes a intron change. The variant allele was found at a frequency of 0.0495 in 152,286 control chromosomes in the GnomAD database, including 399 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 0.049 (399 hom., cov: 33)
• Consequence: LOC124903317 XM_047432035.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903317	XM_047432035.1	c.428+992T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000667337.1	n.1658+992T>G		intron_variant, non_coding_transcript_variant
BMP4	ENST00000559642.1	c.-133+1400A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7527 AN: 152168 Hom.: 400 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0396

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

GnomAD4 genome AF: 0.0495 AC: 7538 AN: 152286 Hom.: 399 Cov.: 33 AF XY: 0.0512 AC XY: 3815 AN XY: 74452

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0374 Hom.: 58

Bravo AF: 0.0517

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	18
Dann	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77671695; hg19: chr14-54424038;