rs16877106

Variant names:

• chr4-25401644-C-T
• rs16877106
• NM_013367.3:c.1215-1327C>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.1215-1327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 152,284 control chromosomes in the GnomAD database, including 205 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 0.048 (205 hom., cov: 32)
• Consequence: ANAPC4 NM_013367.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC4	NM_013367.3	c.1215-1327C>T		intron_variant	Intron 16 of 28	ENST00000315368.8	NP_037499.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC4	ENST00000315368.8	c.1215-1327C>T		intron_variant	Intron 16 of 28	1	NM_013367.3	ENSP00000318775.3
ANAPC4	ENST00000510092.5	c.1215-1327C>T		intron_variant	Intron 16 of 28	5		ENSP00000426654.1
ANAPC4	ENST00000503805.5	n.302-1327C>T		intron_variant	Intron 3 of 7	4
ANAPC4	ENST00000505842.5	n.99-1327C>T		intron_variant	Intron 2 of 7	3

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7368 AN: 152166 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0484 AC: 7372 AN: 152284 Hom.: 205 Cov.: 32 AF XY: 0.0475 AC XY: 3540 AN XY: 74456

African (AFR) AF: 0.0739 AC: 3071 AN: 41544

American (AMR) AF: 0.0305 AC: 467 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.00714 AC: 37 AN: 5182

South Asian (SAS) AF: 0.0777 AC: 375 AN: 4826

European-Finnish (FIN) AF: 0.0298 AC: 316 AN: 10610

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0391 AC: 2657 AN: 68028

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0438 Hom.: 384

Bravo AF: 0.0498

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.55
PhyloP100		-0.21
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: rs16877106; hg19: chr4-25403266;