rs3816587

Variant names:

• chr4-25415622-C-A
• rs3816587
• NM_013367.3:c.1901+82C>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 NM_013367.3(ANAPC4):​c.1901+82C>A variant causes a intron 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 NM_013367.3 intron
• 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).

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>A		intron	N/A	NP_037499.2
	ANAPC4	NM_001286756.2		c.1904+82C>A		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>A		intron	N/A	ENSP00000318775.3	Q9UJX5-1
	ANAPC4	ENST00000504256.5	TSL:1	n.1346C>A		non_coding_transcript_exon	Exon 7 of 8
	ANAPC4	ENST00000510092.5	TSL:5	c.1904+82C>A		intron	N/A	ENSP00000426654.1	Q9UJX5-3

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 v4.9

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;