Genetic Variant APIP:c.58-1718T>C (chr11-34896828-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015957.4(APIP):c.58-1718T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,284,776 control chromosomes in the GnomAD database, including 319,784 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 0.66 ( 33447 hom., cov: 31)

Exomes 𝑓: 0.71 ( 286337 hom. )

Consequence

APIP
NM_015957.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0890

Publications

22 publications found

Variant links:

Genes affected

APIP (HGNC:17581): (APAF1 interacting protein) Enables identical protein binding activity; methylthioribulose 1-phosphate dehydratase activity; and zinc ion binding activity. Involved in several processes, including L-methionine salvage from methylthioadenosine; protein homotetramerization; and pyroptosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

APIP links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (REVEL=0.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
APIP	NM_015957.4 link	c.58-1718T>C		intron_variant	Intron 1 of 6	ENST00000395787.4	NP_057041.2
APIP	XM_011520154.4 link	c.41T>C	p.Val14Ala	missense_variant	Exon 2 of 8		XP_011518456.1
APIP	XM_017017875.3 link	c.-159-1718T>C		intron_variant	Intron 2 of 7		XP_016873364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APIP	ENST00000395787.4 link	c.58-1718T>C		intron_variant	Intron 1 of 6	1	NM_015957.4	ENSP00000379133.3
APIP	ENST00000527830.1 link	n.125-6276T>C		intron_variant	Intron 1 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100187

AN:

151816

Hom.:

33445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.833

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.720

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.656

GnomAD2 exomes

AF:

0.683

AC:

87633

AN:

128244

AF XY:

0.692

show subpopulations

Gnomad AFR exome

AF:

0.537

Gnomad AMR exome

AF:

0.575

Gnomad ASJ exome

AF:

0.740

Gnomad EAS exome

AF:

0.775

Gnomad FIN exome

AF:

0.673

Gnomad NFE exome

AF:

0.718

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.709

AC:

803721

AN:

1132840

Hom.:

286337

Cov.:

AF XY:

0.710

AC XY:

394616

AN XY:

555914

show subpopulations

African (AFR)

AF:

0.533

AC:

12959

AN:

24322

American (AMR)

AF:

0.576

AC:

16263

AN:

28244

Ashkenazi Jewish (ASJ)

AF:

0.743

AC:

11822

AN:

15908

East Asian (EAS)

AF:

0.772

AC:

9888

AN:

12814

South Asian (SAS)

AF:

0.705

AC:

53659

AN:

76108

European-Finnish (FIN)

AF:

0.675

AC:

8530

AN:

12638

Middle Eastern (MID)

AF:

0.737

AC:

3239

AN:

4394

European-Non Finnish (NFE)

AF:

0.717

AC:

657871

AN:

917024

Other (OTH)

AF:

0.713

AC:

29490

AN:

41388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

11210

22420

33629

44839

56049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19038

38076

57114

76152

95190

<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:

0.660

AC:

100222

AN:

151936

Hom.:

33447

Cov.:

AF XY:

0.660

AC XY:

48993

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.545

AC:

22547

AN:

41386

American (AMR)

AF:

0.643

AC:

9823

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

2564

AN:

3466

East Asian (EAS)

AF:

0.760

AC:

3927

AN:

5168

South Asian (SAS)

AF:

0.691

AC:

3329

AN:

4818

European-Finnish (FIN)

AF:

0.672

AC:

7081

AN:

10538

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.715

AC:

48609

AN:

67972

Other (OTH)

AF:

0.649

AC:

1369

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1728

3457

5185

6914

8642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.688

Hom.:

64690

Bravo

AF:

0.649

Asia WGS

AF:

0.697

AC:

2424

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

7.2

(source)

DANN

Benign

0.12

PhyloP100

-0.089

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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