4-67520364-T-C

Variant names:

• chr4-67520364-T-C
• rs355506
• NM_001812.4:c.332-862A>G

Variant summary

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

The NM_001812.4(CENPC):​c.332-862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,952 control chromosomes in the GnomAD database, including 30,452 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 0.63 (30452 hom., cov: 31)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

Genes affected

CENPC (HGNC:1854): (centromere protein C) Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPC	NM_001812.4	c.332-862A>G		intron_variant	Intron 5 of 18	ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11	c.332-862A>G		intron_variant	Intron 5 of 18	1	NM_001812.4	ENSP00000273853.6
CENPC	ENST00000506882.5	n.332-862A>G		intron_variant	Intron 5 of 19	1		ENSP00000426078.1
CENPC	ENST00000510189.5	n.480-862A>G		intron_variant	Intron 5 of 13	1
CENPC	ENST00000513216.5	n.53-862A>G		intron_variant	Intron 1 of 14	5		ENSP00000421234.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95699 AN: 151834 Hom.: 30405 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.630 AC: 95794 AN: 151952 Hom.: 30452 Cov.: 31 AF XY: 0.635 AC XY: 47172 AN XY: 74266

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.673

Alfa AF: 0.608 Hom.: 4087

Bravo AF: 0.645

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.67

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: rs355506; hg19: chr4-68386082;