4-25415622-C-T

Variant names:

• chr4-25415622-C-T
• rs3816587
• NM_013367.3:c.1901+82C>T

Variant summary

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

The NM_013367.3(ANAPC4):​c.1901+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,246,750 control chromosomes in the GnomAD database, including 202,118 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 0.54 (22697 hom., cov: 32)
  • Exomes 𝑓: 0.57 (179421 hom.)
• Consequence: ANAPC4 NM_013367.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 37 publications found

Genes affected

ANAPC4 (HGNC:19990): (anaphase promoting complex subunit 4) A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The exact function of this gene product is not known. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ENSG00000298218 (HGNC:58748):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013367.3. 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
	ANAPC4	NM_013367.3	MANE Select	c.1901+82C>T		intron	N/A	NP_037499.2
	ANAPC4	NM_001286756.2		c.1904+82C>T		intron	N/A	NP_001273685.1	Q9UJX5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC4	ENST00000315368.8	TSL:1 MANE Select	c.1901+82C>T		intron	N/A	ENSP00000318775.3	Q9UJX5-1
	ANAPC4	ENST00000504256.5	TSL:1	n.1346C>T		non_coding_transcript_exon	Exon 7 of 8
	ANAPC4	ENST00000510092.5	TSL:5	c.1904+82C>T		intron	N/A	ENSP00000426654.1	Q9UJX5-3

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82212 AN: 151892 Hom.: 22696 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.568 AC: 622342 AN: 1094740 Hom.: 179421 Cov.: 13 AF XY: 0.564 AC XY: 312082 AN XY: 553460

African (AFR) AF: 0.466 AC: 11924 AN: 25606

American (AMR) AF: 0.531 AC: 17097 AN: 32220

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 13954 AN: 22294

East Asian (EAS) AF: 0.339 AC: 12326 AN: 36320

South Asian (SAS) AF: 0.437 AC: 30296 AN: 69376

European-Finnish (FIN) AF: 0.674 AC: 32445 AN: 48170

Middle Eastern (MID) AF: 0.524 AC: 2094 AN: 3998

European-Non Finnish (NFE) AF: 0.587 AC: 475049 AN: 808910

Other (OTH) AF: 0.568 AC: 27157 AN: 47846

GnomAD4 genome AF: 0.541 AC: 82263 AN: 152010 Hom.: 22697 Cov.: 32 AF XY: 0.542 AC XY: 40299 AN XY: 74334

African (AFR) AF: 0.476 AC: 19709 AN: 41442

American (AMR) AF: 0.539 AC: 8233 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2168 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1613 AN: 5164

South Asian (SAS) AF: 0.423 AC: 2042 AN: 4822

European-Finnish (FIN) AF: 0.671 AC: 7093 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39536 AN: 67954

Other (OTH) AF: 0.552 AC: 1165 AN: 2112

Alfa AF: 0.556 Hom.: 68710

Bravo AF: 0.529

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.44
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3816587; hg19: chr4-25417244;