rs17040773

Variant names:

• chr2-111742458-A-C
• rs17040773
• ENST00000643447.1:n.*97-12137T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643447.1(ANAPC1):​n.*97-12137T>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 37 publications found

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]

CENPNP2 (HGNC:54593): (CENPN pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643447.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC1	ENST00000643447.1		n.*97-12137T>G		intron	N/A	ENSP00000494863.1	A0A2R8YF63
	CENPNP2	ENST00000455969.1	TSL:6	n.-128A>C		upstream_gene	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.106 AC: 7 AN: 66

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.130 AC: 7 AN: 54

Other (OTH) AF: 0.250 AC: 2 AN: 8

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

African (AFR) AF: 0.0608 AC: 2508 AN: 41236

American (AMR) AF: 0.178 AC: 2722 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3468

East Asian (EAS) AF: 0.159 AC: 823 AN: 5170

South Asian (SAS) AF: 0.199 AC: 958 AN: 4808

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10560

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15757 AN: 67950

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.189 Hom.: 775

Bravo AF: 0.169

Asia WGS AF: 0.178 AC: 619 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		0.010

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17040773;

hg19: chr2-112500035;

COSMIC: COSV71938006;