rs3816587

Variant names:

• chr4-25415622-C-A
• rs3816587
• ENST00000504256.5:n.1346C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-25415622-C-A
• chr4-25415622-C-T

Variant summary

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

The ENST00000504256.5(ANAPC4):​n.1346C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,900 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: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: ANAPC4 ENST00000504256.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 0 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: 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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC4	NM_013367.3	c.1901+82C>A		intron_variant	Intron 26 of 28	ENST00000315368.8	NP_037499.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC4	ENST00000315368.8	c.1901+82C>A		intron_variant	Intron 26 of 28	1	NM_013367.3	ENSP00000318775.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097900 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 555010

African (AFR) AF: 0.00 AC: 0 AN: 25692

American (AMR) AF: 0.00 AC: 0 AN: 32298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22334

East Asian (EAS) AF: 0.00 AC: 0 AN: 36362

South Asian (SAS) AF: 0.00 AC: 0 AN: 69550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4012

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 811434

Other (OTH) AF: 0.00 AC: 0 AN: 47980

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.43
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;