4-25415749-G-A

Variant names:

• chr4-25415749-G-A
• rs10517073
• ENST00000504256.5:n.1473G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504256.5(ANAPC4):​n.1473G>A variant causes a non coding transcript exon 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 ENST00000504256.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197
• Publications: 12 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504256.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC4	NM_013367.3	MANE Select	c.1901+209G>A		intron	N/A	NP_037499.2
	ANAPC4	NM_001286756.2		c.1904+209G>A		intron	N/A	NP_001273685.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANAPC4	ENST00000504256.5	TSL:1	n.1473G>A		non_coding_transcript_exon	Exon 7 of 8
	ANAPC4	ENST00000315368.8	TSL:1 MANE Select	c.1901+209G>A		intron	N/A	ENSP00000318775.3
	ANAPC4	ENST00000506973.1	TSL:2	n.598G>A		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AF: 0.567 AC: 4617 AN: 8140

American (AMR) AF: 0.547 AC: 5306 AN: 9698

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 6623 AN: 10446

East Asian (EAS) AF: 0.357 AC: 8437 AN: 23620

South Asian (SAS) AF: 0.449 AC: 7698 AN: 17138

European-Finnish (FIN) AF: 0.683 AC: 16143 AN: 23650

Middle Eastern (MID) AF: 0.551 AC: 844 AN: 1532

European-Non Finnish (NFE) AF: 0.592 AC: 116490 AN: 196890

Other (OTH) AF: 0.580 AC: 11303 AN: 19488

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

African (AFR) AF: 0.575 AC: 23822 AN: 41436

American (AMR) AF: 0.553 AC: 8431 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1612 AN: 5162

South Asian (SAS) AF: 0.425 AC: 2052 AN: 4828

European-Finnish (FIN) AF: 0.671 AC: 7096 AN: 10574

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39613 AN: 67944

Other (OTH) AF: 0.578 AC: 1217 AN: 2106

Alfa AF: 0.575 Hom.: 81560

Bravo AF: 0.564

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.52
PhyloP100		0.20
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: rs10517073; hg19: chr4-25417371;