4-67470253-T-C

Position:

• chr4-67470253-T-C

Variant summary

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

The NM_001812.4(CENPC):​c.*2352A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,944 control chromosomes in the GnomAD database, including 29,946 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 (29918 hom., cov: 30)
  • Exomes 𝑓: 0.62 (28 hom.)
• Consequence: CENPC NM_001812.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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]

CENPC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPC	NM_001812.4	c.*2352A>G		3_prime_UTR_variant	19/19	ENST00000273853.11	NP_001803.2
CENPC	NM_001362481.2	c.*2352A>G		3_prime_UTR_variant	19/19		NP_001349410.1
CENPC	XM_047449526.1	c.*2360A>G		3_prime_UTR_variant	18/18		XP_047305482.1
CENPC	NR_155754.2	n.5450A>G		non_coding_transcript_exon_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853	c.*2352A>G		3_prime_UTR_variant	19/19	1	NM_001812.4	ENSP00000273853.6

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94840 AN: 151666 Hom.: 29877 Cov.: 30

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.619 AC: 99 AN: 160 Hom.: 28 Cov.: 0 AF XY: 0.612 AC XY: 71 AN XY: 116

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.625 AC: 94929 AN: 151784 Hom.: 29918 Cov.: 30 AF XY: 0.630 AC XY: 46741 AN XY: 74160

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.666

Alfa AF: 0.496 Hom.: 1680

Bravo AF: 0.640

Asia WGS AF: 0.768 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.54

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: rs11946612; hg19: chr4-68335971;