rs355461

Positions:

• chr4-67515006-C-A

Variant summary

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

The ENST00000273853.11(CENPC):​c.831-319G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 146,806 control chromosomes in the GnomAD database, including 29,839 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 0.64 (29839 hom., cov: 24)
• Consequence: CENPC ENST00000273853.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPC	NM_001812.4	c.831-319G>T		intron_variant		ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11	c.831-319G>T		intron_variant		1	NM_001812.4	ENSP00000273853	P1
CENPC	ENST00000506882.5	c.831-319G>T		intron_variant, NMD_transcript_variant		1		ENSP00000426078
CENPC	ENST00000510189.5	n.979-319G>T		intron_variant, non_coding_transcript_variant		1
CENPC	ENST00000513216.5	c.552-319G>T		intron_variant, NMD_transcript_variant		5		ENSP00000421234

Frequencies

GnomAD3 genomes AF: 0.640 AC: 93941 AN: 146726 Hom.: 29801 Cov.: 24

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.640 AC: 94013 AN: 146806 Hom.: 29839 Cov.: 24 AF XY: 0.649 AC XY: 46149 AN XY: 71152

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.685

Alfa AF: 0.608 Hom.: 4086

Bravo AF: 0.645

Asia WGS AF: 0.765 AC: 2630 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
DANN	Benign	0.53

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: rs355461; hg19: chr4-68380724;