rs12651029

Positions:

• chr4-144849015-G-A

Variant summary

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

The ENST00000649263.1(ENSG00000285713):​n.327+215557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 149,968 control chromosomes in the GnomAD database, including 4,235 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 (4235 hom., cov: 27)
• Consequence: ENSG00000285713 ENST00000649263.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

Genes affected

ENSG00000285713 (HGNC:):

ANAPC10 (HGNC:24077): (anaphase promoting complex subunit 10) ANAPC10 is a core subunit of the anaphase-promoting complex (APC), or cyclosome, a ubiquitin protein ligase that is essential for progression through the cell cycle. APC initiates sister chromatid separation by ubiquitinating the anaphase inhibitor securin (PTTG1; MIM 604147) and triggers exit from mitosis by ubiquitinating cyclin B (CCNB1; MIM 123836), the activating subunit of cyclin-dependent kinase-1 (CDK1; MIM 116940) (summary by Wendt et al., 2001 [PubMed 11524682]).[supplied by OMIM, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.144849015G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285713	ENST00000649263.1	n.327+215557C>T		intron_variant				ENSP00000497507.1
ANAPC10	ENST00000641499.1	n.*55-16097C>T		intron_variant				ENSP00000493135.1
ENSG00000285783	ENST00000650526.1	n.93+21846C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32646 AN: 149858 Hom.: 4231 Cov.: 27

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.218 AC: 32644 AN: 149968 Hom.: 4235 Cov.: 27 AF XY: 0.218 AC XY: 15923 AN XY: 73106

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.233

Alfa AF: 0.274 Hom.: 11935

Bravo AF: 0.210

Asia WGS AF: 0.213 AC: 740 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12651029; hg19: chr4-145770167;