ENST00000643447.1:n.*139+45425C>T

Variant names:

• chr2-111684854-G-A
• rs9308631
• ENST00000643447.1:n.*139+45425C>T

Variant summary

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

The ENST00000643447.1(ANAPC1):​n.*139+45425C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 3 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]

ANAPC1 Gene-Disease associations (from GenCC):

• Rothmund-Thomson syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000285016 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC1	ENST00000643447.1	n.*139+45425C>T		intron_variant	Intron 9 of 11			ENSP00000494863.1
ENSG00000285016	ENST00000644013.1	n.68+14112C>T		intron_variant	Intron 1 of 7

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

African (AFR) AF: 0.754 AC: 31251 AN: 41468

American (AMR) AF: 0.634 AC: 9692 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2059 AN: 3464

East Asian (EAS) AF: 0.603 AC: 3124 AN: 5178

South Asian (SAS) AF: 0.615 AC: 2966 AN: 4820

European-Finnish (FIN) AF: 0.588 AC: 6213 AN: 10560

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.616 AC: 41870 AN: 67992

Other (OTH) AF: 0.631 AC: 1334 AN: 2114

Alfa AF: 0.625 Hom.: 21468

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
PhyloP100		-3.5

Splicing

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

Other links and lift over

dbSNP: rs9308631; hg19: chr2-112442431;