dbSNP rs10517073: ANAPC4:n.1473G>A (chr4-25415749-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.197

Publications

12 publications found

Variant links:

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]

ANAPC4 links:

ENSG00000298218 (HGNC:58748):

ENSG00000298218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANAPC4	NM_013367.3 link	c.1901+209G>A	intron_variant	Intron 26 of 28	ENST00000315368.8	NP_037499.2	Q9UJX5-1
ANAPC4	NM_001286756.2 link	c.1904+209G>A	intron_variant	Intron 26 of 28		NP_001273685.1	Q9UJX5-3B3KN47
ANAPC4	XM_011513838.2 link	c.1568+209G>A	intron_variant	Intron 24 of 26		XP_011512140.1
ANAPC4	XM_005248159.2 link	c.800+209G>A	intron_variant	Intron 13 of 15		XP_005248216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC4	ENST00000315368.8 link	c.1901+209G>A		intron_variant	Intron 26 of 28	1	NM_013367.3	ENSP00000318775.3		Q9UJX5-1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86675

AN:

151864

Hom.:

25037

Cov.:

show subpopulations

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.:

AF XY:

0.567

AC XY:

91543

AN XY:

161576

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

3487

6973

10460

13946

17433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.571

AC:

86741

AN:

151982

Hom.:

25051

Cov.:

AF XY:

0.571

AC XY:

42431

AN XY:

74280

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1890

3780

5671

7561

9451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.7

(source)

DANN

Benign

0.52

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over