4-67530807-G-C

Variant names:

• chr4-67530807-G-C
• rs355477
• NM_001812.4:c.331+8C>G

Variant summary

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

The NM_001812.4(CENPC):​c.331+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,478,304 control chromosomes in the GnomAD database, including 284,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (30789 hom., cov: 32)
  • Exomes 𝑓: 0.62 (253956 hom.)
• Consequence: CENPC NM_001812.4 splice_region, intron
• Scores: Splicing: ADA: 0.0006775
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001812.4. 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
	CENPC	NM_001812.4	MANE Select	c.331+8C>G		splice_region intron	N/A	NP_001803.2
	CENPC	NM_001362481.2		c.331+8C>G		splice_region intron	N/A	NP_001349410.1
	CENPC	NR_155754.2		n.479+8C>G		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	ENST00000273853.11	TSL:1 MANE Select	c.331+8C>G		splice_region intron	N/A	ENSP00000273853.6
	CENPC	ENST00000506882.5	TSL:1	n.331+8C>G		splice_region intron	N/A	ENSP00000426078.1
	CENPC	ENST00000510189.5	TSL:1	n.479+8C>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96239 AN: 151844 Hom.: 30743 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.671

GnomAD2 exomes AF: 0.639 AC: 133129 AN: 208350 AF XY: 0.634

Gnomad AFR exome AF: 0.625

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.639

Gnomad EAS exome AF: 0.809

Gnomad FIN exome AF: 0.564

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.633

GnomAD4 exome AF: 0.616 AC: 816423 AN: 1326346 Hom.: 253956 Cov.: 18 AF XY: 0.617 AC XY: 409231 AN XY: 663766

African (AFR) AF: 0.647 AC: 19100 AN: 29518

American (AMR) AF: 0.782 AC: 28314 AN: 36202

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 15557 AN: 24342

East Asian (EAS) AF: 0.793 AC: 29796 AN: 37582

South Asian (SAS) AF: 0.673 AC: 51791 AN: 77012

European-Finnish (FIN) AF: 0.569 AC: 29672 AN: 52136

Middle Eastern (MID) AF: 0.717 AC: 3913 AN: 5456

European-Non Finnish (NFE) AF: 0.598 AC: 602928 AN: 1008540

Other (OTH) AF: 0.636 AC: 35352 AN: 55558

GnomAD4 genome AF: 0.634 AC: 96333 AN: 151958 Hom.: 30789 Cov.: 32 AF XY: 0.639 AC XY: 47453 AN XY: 74256

African (AFR) AF: 0.642 AC: 26615 AN: 41434

American (AMR) AF: 0.735 AC: 11225 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2188 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4200 AN: 5172

South Asian (SAS) AF: 0.697 AC: 3356 AN: 4818

European-Finnish (FIN) AF: 0.568 AC: 5974 AN: 10520

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40640 AN: 67964

Other (OTH) AF: 0.674 AC: 1418 AN: 2104

Alfa AF: 0.584 Hom.: 7137

Bravo AF: 0.649

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00068
dbscSNV1_RF	Benign	0.014
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: rs355477; hg19: chr4-68396525; COSMIC: COSV56625490;