dbSNP rs1800247: PMF1-BGLAP:c.565-519T>C (chr1-156242034-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001199661.1(PMF1-BGLAP):c.504-519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 621,846 control chromosomes in the GnomAD database, including 14,334 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 0.21 ( 3273 hom., cov: 32)

Exomes 𝑓: 0.21 ( 11061 hom. )

Consequence

PMF1-BGLAP
NM_001199661.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Variant links:

Genes affected

PMF1-BGLAP (HGNC:42953): (PMF1-BGLAP readthrough) This locus represents naturally occurring read-through transcription between the neighboring PMF1 (polyamine-modulated factor 1) and BGLAP (bone gamma-carboxyglutamate Gla protein) genes on chromosome 1. Alternative splicing results in multiple transcript variants encoding isoforms that share sequence identity with the upstream gene product, but they contain distinct C-termini due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

PMF1-BGLAP links:

BGLAP (HGNC:1043): (bone gamma-carboxyglutamate protein) This gene encodes a highly abundant bone protein secreted by osteoblasts that regulates bone remodeling and energy metabolism. The encoded protein contains a Gla (gamma carboxyglutamate) domain, which functions in binding to calcium and hydroxyapatite, the mineral component of bone. Serum osteocalcin levels may be negatively correlated with metabolic syndrome. Read-through transcription exists between this gene and the neighboring upstream gene, PMF1 (polyamine-modulated factor 1), but the encoded protein only shows sequence identity with the upstream gene product. [provided by RefSeq, Jun 2015]

BGLAP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BGLAP	NM_199173.6 link	c.-198T>C		upstream_gene_variant		ENST00000368272.5	NP_954642.1	P02818

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMF1-BGLAP	ENST00000490491.5 link	c.565-519T>C		intron_variant	Intron 4 of 6	2		ENSP00000475561.1		U3KQ54
BGLAP	ENST00000368272.5 link	c.-198T>C		upstream_gene_variant		1	NM_199173.6	ENSP00000357255.4		P02818

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31290

AN:

151796

Hom.:

3273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.213

AC:

99983

AN:

469930

Hom.:

11061

Cov.:

AF XY:

0.215

AC XY:

52566

AN XY:

244664

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.206

AC:

31286

AN:

151916

Hom.:

3273

Cov.:

AF XY:

0.202

AC XY:

15005

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.208

Hom.:

969

Bravo

AF:

0.211

Asia WGS

AF:

0.249

AC:

865

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.8

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over