4-67544895-T-C

Variant names:

• chr4-67544895-T-C
• rs13135430
• NM_001812.4:c.18+443A>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.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
• Publications: 2 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 (SAS) allele frequency at 95% confidence interval = 0.254 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	NM_001812.4	MANE Select	c.18+443A>G		intron	N/A	NP_001803.2	Q03188-1
	CENPC	NM_001362481.2		c.18+443A>G		intron	N/A	NP_001349410.1
	CENPC	NR_155754.2		n.166+443A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPC	ENST00000273853.11	TSL:1 MANE Select	c.18+443A>G		intron	N/A	ENSP00000273853.6	Q03188-1
	CENPC	ENST00000506882.5	TSL:1	n.18+443A>G		intron	N/A	ENSP00000426078.1	Q03188-2
	CENPC	ENST00000510189.5	TSL:1	n.166+443A>G		intron	N/A

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

African (AFR) AF: 0.188 AC: 7783 AN: 41430

American (AMR) AF: 0.177 AC: 2699 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 839 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1095 AN: 5176

South Asian (SAS) AF: 0.267 AC: 1284 AN: 4818

European-Finnish (FIN) AF: 0.309 AC: 3253 AN: 10540

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15385 AN: 67992

Other (OTH) AF: 0.200 AC: 421 AN: 2104

Alfa AF: 0.208 Hom.: 1952

Bravo AF: 0.204

Asia WGS AF: 0.195 AC: 677 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	0.54
DANN	Benign	0.31
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13135430; hg19: chr4-68410613;