4-67544895-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.18+443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,018 control chromosomes in the GnomAD database, including 3,603 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 0.22 (3603 hom., cov: 32)
• Consequence: CENPC NM_001812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPC	NM_001812.4	c.18+443A>G		intron_variant		ENST00000273853.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPC	ENST00000273853.11	c.18+443A>G		intron_variant		1	NM_001812.4	P1
CENPC	ENST00000506882.5	c.18+443A>G		intron_variant, NMD_transcript_variant		1
CENPC	ENST00000510189.5	n.166+443A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32909 AN: 151896 Hom.: 3608 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.217 AC: 32914 AN: 152018 Hom.: 3603 Cov.: 32 AF XY: 0.222 AC XY: 16465 AN XY: 74308

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.200

Alfa AF: 0.205 Hom.: 1698

Bravo AF: 0.204

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.54
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13135430; hg19: chr4-68410613;