chr2-111712578-C-T

Variant names:

• chr2-111712578-C-T
• rs11122895
• ENST00000643447.1:n.*139+17701G>A

Variant summary

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

The ENST00000643447.1(ANAPC1):​n.*139+17701G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,192 control chromosomes in the GnomAD database, including 8,240 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 0.31 (8240 hom., cov: 33)
• Consequence: ANAPC1 ENST00000643447.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 7 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 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+17701G>A		intron_variant	Intron 9 of 11			ENSP00000494863.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47045 AN: 152074 Hom.: 8242 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.309 AC: 47054 AN: 152192 Hom.: 8240 Cov.: 33 AF XY: 0.306 AC XY: 22792 AN XY: 74388

African (AFR) AF: 0.164 AC: 6820 AN: 41550

American (AMR) AF: 0.287 AC: 4394 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3468

East Asian (EAS) AF: 0.150 AC: 776 AN: 5176

South Asian (SAS) AF: 0.311 AC: 1495 AN: 4808

European-Finnish (FIN) AF: 0.340 AC: 3601 AN: 10590

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27383 AN: 67980

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.297 Hom.: 1437

Bravo AF: 0.298

Asia WGS AF: 0.219 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.77
PhyloP100		-0.040

Splicing

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

Other links and lift over

dbSNP: rs11122895; hg19: chr2-112470155;