chr1-156240066-C-G

Variant names:

• chr1-156240066-C-G
• rs1543294
• ENST00000490491.5:c.565-2487C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000490491.5(PMF1-BGLAP):​c.565-2487C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PMF1-BGLAP ENST00000490491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 21 publications found

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 (HGNC:9112): (polyamine modulated factor 1) Enables leucine zipper domain binding activity and transcription coactivator activity. Involved in chromosome segregation. Located in Golgi apparatus; kinetochore; and nucleoplasm. Part of MIS12/MIND type complex. Implicated in bladder carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1-BGLAP	NM_001199661.1		c.504-2487C>G		intron	N/A	NP_001186590.1
	PMF1-BGLAP	NM_001199662.1		c.565-2487C>G		intron	N/A	NP_001186591.1
	PMF1-BGLAP	NM_001199663.1		c.369-2487C>G		intron	N/A	NP_001186592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1-BGLAP	ENST00000490491.5	TSL:2	c.565-2487C>G		intron	N/A	ENSP00000475561.1
	PMF1-BGLAP	ENST00000320139.5	TSL:1	c.369-2487C>G		intron	N/A	ENSP00000324909.5
	PMF1-BGLAP	ENST00000368276.8	TSL:3	c.504-2487C>G		intron	N/A	ENSP00000357259.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 5028 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2778

African (AFR) AF: 0.00 AC: 0 AN: 106

American (AMR) AF: 0.00 AC: 0 AN: 174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 118

East Asian (EAS) AF: 0.00 AC: 0 AN: 142

South Asian (SAS) AF: 0.00 AC: 0 AN: 486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3466

Other (OTH) AF: 0.00 AC: 0 AN: 286

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		0.12

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

Other links and lift over

dbSNP: rs1543294; hg19: chr1-156209857;