7-33905022-G-A

Variant summary

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

The ENST00000297161.6(BMPER):c.-263G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 156,438 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (1 hom.)
• Consequence: BMPER ENST00000297161.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.710

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=-0.7).
• BP6: Variant 7-33905022-G-A is Benign according to our data. Variant chr7-33905022-G-A is described in ClinVar as [Benign]. Clinvar id is 360086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPER	NM_133468.5	c.-263G>A		5_prime_UTR_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPER	ENST00000297161.6	c.-263G>A		5_prime_UTR_variant	1/16	1		P1
BMPER	ENST00000448280.5	n.112G>A		non_coding_transcript_exon_variant	1/4	3
BMPER	ENST00000436222.6	n.235+480G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00712 AC: 1083 AN: 152180 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.00764

GnomAD4 exome AF: 0.00483 AC: 20 AN: 4140 Hom.: 1 Cov.: 0 AF XY: 0.00553 AC XY: 11 AN XY: 1988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00420

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00245

Gnomad4 OTH exome AF: 0.00901

GnomAD4 genome AF: 0.00711 AC: 1083 AN: 152298 Hom.: 45 Cov.: 32 AF XY: 0.00790 AC XY: 588 AN XY: 74474

Gnomad4 AFR AF: 0.00493

Gnomad4 AMR AF: 0.00398

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.000479 Hom.: 0

Bravo AF: 0.00767

Asia WGS AF: 0.0490 AC: 168 AN: 3476

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 13, 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	-0.70
Cadd	Benign	4.7
Dann	Benign	0.95

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: rs117405942; hg19: chr7-33944634;