7-33904972-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000297161.6(BMPER):c.-313G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 153,590 control chromosomes in the GnomAD database, including 355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (353 hom., cov: 32)
  • Exomes 𝑓: 0.019 (2 hom.)
• Consequence: BMPER ENST00000297161.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636

Genes affected

BMPER (HGNC:24154): (BMP binding endothelial regulator) This gene encodes a secreted protein that interacts with, and inhibits bone morphogenetic protein (BMP) function. It has been shown to inhibit BMP2- and BMP4-dependent osteoblast differentiation and BMP-dependent differentiation of the chondrogenic cells. Mutations in this gene are associated with a lethal skeletal disorder, diaphanospondylodysostosis. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-33904972-G-C is Benign according to our data. Variant chr7-33904972-G-C is described in ClinVar as [Benign]. Clinvar id is 360085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPER	NM_133468.5	c.-313G>C		5_prime_UTR_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPER	ENST00000297161.6	c.-313G>C		5_prime_UTR_variant	1/16	1		P1
BMPER	ENST00000448280.5	n.62G>C		non_coding_transcript_exon_variant	1/4	3
BMPER	ENST00000436222.6	n.235+430G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7866 AN: 152188 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.0187 AC: 24 AN: 1284 Hom.: 2 Cov.: 0 AF XY: 0.0230 AC XY: 18 AN XY: 782

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.0600

GnomAD4 genome AF: 0.0519 AC: 7911 AN: 152306 Hom.: 353 Cov.: 32 AF XY: 0.0533 AC XY: 3970 AN XY: 74482

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0755

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0856

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.00740 Hom.: 0

Bravo AF: 0.0548

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Diaphanospondylodysostosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	5.5
Dann	Benign	0.82

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: rs114417992; hg19: chr7-33944584;