chr2-111705378-G-C

Position:

• chr2-111705378-G-C

Variant summary

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

The ENST00000643447.1(ANAPC1):​c.*139+24901C>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 0.161 in 152,172 control chromosomes in the GnomAD database, including 1,990 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 0.16 (1990 hom., cov: 32)
• Consequence: ANAPC1 ENST00000643447.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 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+24901C>G		intron_variant, NMD_transcript_variant				ENSP00000494863

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24474 AN: 152054 Hom.: 1991 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.161 AC: 24484 AN: 152172 Hom.: 1990 Cov.: 32 AF XY: 0.162 AC XY: 12074 AN XY: 74382

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0742 Hom.: 95

Bravo AF: 0.161

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.018
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3906021; hg19: chr2-112462955;