rs3816587

Positions:

• chr4-25415622-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC4	NM_013367.3	c.1901+82C>T		intron_variant		ENST00000315368.8	NP_037499.2
ANAPC4	NM_001286756.2	c.1904+82C>T		intron_variant			NP_001273685.1
ANAPC4	XM_011513838.2	c.1568+82C>T		intron_variant			XP_011512140.1
ANAPC4	XM_005248159.2	c.800+82C>T		intron_variant			XP_005248216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC4	ENST00000315368.8	c.1901+82C>T		intron_variant		1	NM_013367.3	ENSP00000318775.3

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

Gnomad4 AFR exome AF: 0.466

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.568

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

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.552

Alfa AF: 0.562 Hom.: 45223

Bravo AF: 0.529

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.44
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

Publications

LitVar

Other links and lift over

dbSNP: rs3816587; hg19: chr4-25417244;