chr4-67515006-C-A

Variant names:

• chr4-67515006-C-A
• rs355461
• NM_001812.4:c.831-319G>T

Variant summary

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

The NM_001812.4(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 NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 4 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=-0.87).
• 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 rank	MANE	Protein	UniProt
CENPC	NM_001812.4	c.831-319G>T		intron_variant	Intron 7 of 18	ENST00000273853.11	NP_001803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPC	ENST00000273853.11	c.831-319G>T		intron_variant	Intron 7 of 18	1	NM_001812.4	ENSP00000273853.6
CENPC	ENST00000506882.5	n.831-319G>T		intron_variant	Intron 7 of 19	1		ENSP00000426078.1
CENPC	ENST00000510189.5	n.979-319G>T		intron_variant	Intron 7 of 13	1
CENPC	ENST00000513216.5	n.552-319G>T		intron_variant	Intron 3 of 14	5		ENSP00000421234.1

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

African (AFR) AF: 0.643 AC: 25537 AN: 39736

American (AMR) AF: 0.747 AC: 10913 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2178 AN: 3444

East Asian (EAS) AF: 0.818 AC: 4113 AN: 5028

South Asian (SAS) AF: 0.708 AC: 3304 AN: 4664

European-Finnish (FIN) AF: 0.607 AC: 5531 AN: 9114

Middle Eastern (MID) AF: 0.754 AC: 205 AN: 272

European-Non Finnish (NFE) AF: 0.602 AC: 40338 AN: 67002

Other (OTH) AF: 0.685 AC: 1391 AN: 2032

Alfa AF: 0.608 Hom.: 4235

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs355461; hg19: chr4-68380724;