rs9308631

Positions:

• chr2-111684854-G-A

Variant summary

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

The ENST00000643447.1(ANAPC1):​c.*139+45425C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,092 control chromosomes in the GnomAD database, including 32,799 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 0.65 (32799 hom., cov: 33)
• Consequence: ANAPC1 ENST00000643447.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50

Genes affected

ANAPC1 (HGNC:19988): (anaphase promoting complex subunit 1) This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation. [provided by RefSeq, Dec 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 (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC1	ENST00000643447.1	c.*139+45425C>T		intron_variant, NMD_transcript_variant				ENSP00000494863

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99232 AN: 151974 Hom.: 32755 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.653 AC: 99334 AN: 152092 Hom.: 32799 Cov.: 33 AF XY: 0.653 AC XY: 48570 AN XY: 74330

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.631

Alfa AF: 0.626 Hom.: 14897

Bravo AF: 0.661

Asia WGS AF: 0.603 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9308631; hg19: chr2-112442431;