ENST00000643447.1:n.*139+17701G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000643447.1(ANAPC1):​n.*139+17701G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000046 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000046 (0 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, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.*139+17701G>T		intron	N/A	ENSP00000494863.1	A0A2R8YF63

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74408

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68002

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00 Hom.: 1437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.79
PhyloP100		-0.040

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: rs11122895;

hg19: chr2-112470155;