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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015957.4. 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
	APIP	NM_015957.4	MANE Select	c.58-1718T>C		intron	N/A	NP_057041.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APIP	ENST00000395787.4	TSL:1 MANE Select	c.58-1718T>C		intron	N/A	ENSP00000379133.3
	APIP	ENST00000527830.1	TSL:2	n.125-6276T>C		intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over