chr2-111742458-A-C

Position:

• chr2-111742458-A-C

Variant summary

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

The ENST00000643447.1(ANAPC1):​c.*97-12137T>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,888 control chromosomes in the GnomAD database, including 2,703 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 0.17 (2702 hom., cov: 29)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: ANAPC1 ENST00000643447.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 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.*97-12137T>G		intron_variant, NMD_transcript_variant				ENSP00000494863

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25993 AN: 151636 Hom.: 2702 Cov.: 29

Gnomad AFR AF: 0.0608

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.130 AC: 18 AN: 138 Hom.: 1 AF XY: 0.156 AC XY: 15 AN XY: 96

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.171 AC: 26002 AN: 151750 Hom.: 2702 Cov.: 29 AF XY: 0.169 AC XY: 12550 AN XY: 74172

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.202

Alfa AF: 0.204 Hom.: 775

Bravo AF: 0.169

Asia WGS AF: 0.178 AC: 619 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17040773; hg19: chr2-112500035; COSMIC: COSV71938006;