1-156240066-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490491.5(PMF1-BGLAP):​c.565-2487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 157,184 control chromosomes in the GnomAD database, including 4,059 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 0.22 (3953 hom., cov: 32)
  • Exomes 𝑓: 0.19 (106 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

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>T		intron	N/A	NP_001186590.1
	PMF1-BGLAP	NM_001199662.1		c.565-2487C>T		intron	N/A	NP_001186591.1
	PMF1-BGLAP	NM_001199663.1		c.369-2487C>T		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>T		intron	N/A	ENSP00000475561.1
	PMF1-BGLAP	ENST00000320139.5	TSL:1	c.369-2487C>T		intron	N/A	ENSP00000324909.5
	PMF1-BGLAP	ENST00000368276.8	TSL:3	c.504-2487C>T		intron	N/A	ENSP00000357259.4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33585 AN: 152054 Hom.: 3936 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.187 AC: 935 AN: 5012 Hom.: 106 Cov.: 0 AF XY: 0.191 AC XY: 529 AN XY: 2770

African (AFR) AF: 0.106 AC: 11 AN: 104

American (AMR) AF: 0.374 AC: 65 AN: 174

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 20 AN: 118

East Asian (EAS) AF: 0.232 AC: 33 AN: 142

South Asian (SAS) AF: 0.212 AC: 103 AN: 486

European-Finnish (FIN) AF: 0.109 AC: 26 AN: 238

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.181 AC: 624 AN: 3452

Other (OTH) AF: 0.171 AC: 49 AN: 286

GnomAD4 genome AF: 0.221 AC: 33636 AN: 152172 Hom.: 3953 Cov.: 32 AF XY: 0.220 AC XY: 16394 AN XY: 74386

African (AFR) AF: 0.198 AC: 8203 AN: 41530

American (AMR) AF: 0.320 AC: 4894 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 865 AN: 3466

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5168

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1183 AN: 10596

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15026 AN: 67986

Other (OTH) AF: 0.231 AC: 488 AN: 2116

Alfa AF: 0.228 Hom.: 10128

Bravo AF: 0.237

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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;