chr7-33905074-G-A

Position:

• chr7-33905074-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.-211G>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 0.0275 in 158,402 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (143 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (0 hom.)
• Consequence: BMPER ENST00000297161.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59

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=-0.59).
• BP6: Variant 7-33905074-G-A is Benign according to our data. Variant chr7-33905074-G-A is described in ClinVar as [Benign]. Clinvar id is 360088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPER	NM_133468.5	c.-211G>A		5_prime_UTR_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPER	ENST00000297161.6	c.-211G>A		5_prime_UTR_variant	1/16	1		P1
BMPER	ENST00000448280.5	n.164G>A		non_coding_transcript_exon_variant	1/4	3
BMPER	ENST00000436222.6	n.235+532G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 4319 AN: 152038 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.0355

Gnomad NFE AF: 0.00418

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00448 AC: 28 AN: 6246 Hom.: 0 Cov.: 0 AF XY: 0.00477 AC XY: 14 AN XY: 2936

Gnomad4 AFR exome AF: 0.0417

Gnomad4 AMR exome AF: 0.0243

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0238

Gnomad4 SAS exome AF: 0.00943

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0285 AC: 4333 AN: 152156 Hom.: 143 Cov.: 32 AF XY: 0.0283 AC XY: 2103 AN XY: 74386

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.00418

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.00137 Hom.: 1

Bravo AF: 0.0335

Asia WGS AF: 0.0480 AC: 167 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	-0.59
CADD	Benign	15
DANN	Benign	0.96

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: rs112890951; hg19: chr7-33944686;