rs10517073

chr4-25415749-G-A

Variant summary

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

The NM_013367.3(ANAPC4):c.1901+209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 462,584 control chromosomes in the GnomAD database, including 76,620 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 0.57 (25051 hom., cov: 32)
  • Exomes 𝑓: 0.57 (51569 hom.)
• Consequence: ANAPC4 NM_013367.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANAPC4	NM_013367.3	c.1901+209G>A		intron_variant		ENST00000315368.8
ANAPC4	NM_001286756.2	c.1904+209G>A		intron_variant
ANAPC4	XM_005248159.2	c.800+209G>A		intron_variant
ANAPC4	XM_011513838.2	c.1568+209G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANAPC4	ENST00000315368.8	c.1901+209G>A		intron_variant		1	NM_013367.3	P4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86675 AN: 151864 Hom.: 25037 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.582

GnomAD4 exome AF: 0.571 AC: 177461 AN: 310602 Hom.: 51569 Cov.: 4 AF XY: 0.567 AC XY: 91543 AN XY: 161576

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.592

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.571 AC: 86741 AN: 151982 Hom.: 25051 Cov.: 32 AF XY: 0.571 AC XY: 42431 AN XY: 74280

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.578

Alfa AF: 0.574 Hom.: 52293

Bravo AF: 0.564

Asia WGS AF: 0.392 AC: 1363 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	6.7
Dann	Benign	0.52

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: rs10517073; hg19: chr4-25417371;