Genetic Variant APIP:c.630-36G>A (chr11-34882852-C-T) – 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.630-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,407,628 control chromosomes in the GnomAD database, including 316,135 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 0.60 ( 28461 hom., cov: 31)

Exomes 𝑓: 0.67 ( 287674 hom. )

Consequence

APIP
NM_015957.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

12 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 (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
APIP	NM_015957.4 link	c.630-36G>A	intron_variant	Intron 6 of 6	ENST00000395787.4	NP_057041.2	Q96GX9-1
APIP	XM_011520154.4 link	c.681-36G>A	intron_variant	Intron 7 of 7		XP_011518456.1
APIP	XM_017017875.3 link	c.414-36G>A	intron_variant	Intron 7 of 7		XP_016873364.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
APIP	ENST00000395787.4 link	c.630-36G>A	intron_variant	Intron 6 of 6	1	NM_015957.4	ENSP00000379133.3	Q96GX9-1
APIP	ENST00000532428.6 link	n.489-36G>A	intron_variant	Intron 4 of 7	1		ENSP00000474191.1	S4R3D6
APIP	ENST00000527830.1 link	n.596-36G>A	intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91288

AN:

151850

Hom.:

28466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.833

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.597

GnomAD2 exomes

AF:

0.643

AC:

149717

AN:

232724

AF XY:

0.650

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.539

Gnomad ASJ exome

AF:

0.683

Gnomad EAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.656

Gnomad NFE exome

AF:

0.686

Gnomad OTH exome

AF:

0.648

GnomAD4 exome

AF:

0.675

AC:

847080

AN:

1255660

Hom.:

287674

Cov.:

AF XY:

0.673

AC XY:

427266

AN XY:

634412

show subpopulations

African (AFR)

AF:

0.408

AC:

11518

AN:

28226

American (AMR)

AF:

0.551

AC:

22403

AN:

40694

Ashkenazi Jewish (ASJ)

AF:

0.682

AC:

16527

AN:

24222

East Asian (EAS)

AF:

0.725

AC:

27208

AN:

37552

South Asian (SAS)

AF:

0.627

AC:

48815

AN:

77908

European-Finnish (FIN)

AF:

0.657

AC:

34534

AN:

52564

Middle Eastern (MID)

AF:

0.664

AC:

3537

AN:

5326

European-Non Finnish (NFE)

AF:

0.691

AC:

647337

AN:

936136

Other (OTH)

AF:

0.664

AC:

35201

AN:

53032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12876

25752

38627

51503

64379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15478

30956

46434

61912

77390

<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:

0.601

AC:

91310

AN:

151968

Hom.:

28461

Cov.:

AF XY:

0.602

AC XY:

44702

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.411

AC:

17037

AN:

41428

American (AMR)

AF:

0.607

AC:

9277

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.687

AC:

2383

AN:

3470

East Asian (EAS)

AF:

0.744

AC:

3852

AN:

5176

South Asian (SAS)

AF:

0.616

AC:

2967

AN:

4820

European-Finnish (FIN)

AF:

0.652

AC:

6877

AN:

10540

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.688

AC:

46718

AN:

67948

Other (OTH)

AF:

0.591

AC:

1245

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1759

3518

5278

7037

8796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.623

Hom.:

9041

Bravo

AF:

0.589

Asia WGS

AF:

0.660

AC:

2296

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.014

(source)

DANN

Benign

0.73

PhyloP100

-1.4

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

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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