rs4848821

Positions:

• chr2-111869196-C-G

Variant summary

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

The NM_022662.4(ANAPC1):​c.612-1100G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,184 control chromosomes in the GnomAD database, including 901 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 0.11 (901 hom., cov: 33)
• Consequence: ANAPC1 NM_022662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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 (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC1	NM_022662.4	c.612-1100G>C		intron_variant		ENST00000341068.8	NP_073153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC1	ENST00000341068.8	c.612-1100G>C		intron_variant		1	NM_022662.4	ENSP00000339109.3
ANAPC1	ENST00000451367.3	n.*61-1100G>C		intron_variant		5		ENSP00000405375.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16335 AN: 152066 Hom.: 894 Cov.: 33

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0734

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0969

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

GnomAD4 genome AF: 0.107 AC: 16359 AN: 152184 Hom.: 901 Cov.: 33 AF XY: 0.109 AC XY: 8091 AN XY: 74400

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0734

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.101

Alfa AF: 0.108 Hom.: 111

Bravo AF: 0.108

Asia WGS AF: 0.135 AC: 467 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	0.49
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4848821; hg19: chr2-112626773;