chr8-18020240-C-G

Position:

• chr8-18020240-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006197.4(PCM1):​c.5842-5121C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,960 control chromosomes in the GnomAD database, including 17,482 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 0.45 (17482 hom., cov: 32)
• Consequence: PCM1 NM_006197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798

Genes affected

PCM1 (HGNC:8727): (pericentriolar material 1) The protein encoded by this gene is a component of centriolar satellites, which are electron dense granules scattered around centrosomes. Inhibition studies show that this protein is essential for the correct localization of several centrosomal proteins, and for anchoring microtubules to the centrosome. Chromosomal aberrations involving this gene are associated with papillary thyroid carcinomas and a variety of hematological malignancies, including atypical chronic myeloid leukemia and T-cell lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PCM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCM1	NM_006197.4	c.5842-5121C>G		intron_variant		ENST00000325083.13	NP_006188.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCM1	ENST00000325083.13	c.5842-5121C>G		intron_variant		1	NM_006197.4	ENSP00000327077.8

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69045 AN: 151842 Hom.: 17478 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 69051 AN: 151960 Hom.: 17482 Cov.: 32 AF XY: 0.447 AC XY: 33179 AN XY: 74266

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.476

Alfa AF: 0.373 Hom.: 1097

Bravo AF: 0.435

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.44

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: rs2237851; hg19: chr8-17877749;