4-25401644-C-T

Position:

• chr4-25401644-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000315368.8(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 ENST00000315368.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.85).
• 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/exons	MANE	Protein	UniProt
ANAPC4	NM_013367.3	c.1215-1327C>T		intron_variant		ENST00000315368.8	NP_037499.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC4	ENST00000315368.8	c.1215-1327C>T		intron_variant		1	NM_013367.3	ENSP00000318775	P4
ANAPC4	ENST00000510092.5	c.1215-1327C>T		intron_variant		5		ENSP00000426654	A1
ANAPC4	ENST00000503805.5	n.302-1327C>T		intron_variant, non_coding_transcript_variant		4
ANAPC4	ENST00000505842.5	n.99-1327C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0739

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.00714

Gnomad4 SAS AF: 0.0777

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0391

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0409 Hom.: 200

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

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: rs16877106; hg19: chr4-25403266;