dbSNP rs2273740: XPNPEP1:c.1242-10T>G (chr10-109877877-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_020383.4(XPNPEP1):c.1242-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,996 control chromosomes in the GnomAD database, including 31,642 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 0.20 ( 3644 hom., cov: 33)

Exomes 𝑓: 0.18 ( 27998 hom. )

Consequence

XPNPEP1
NM_020383.4 intron

Scores

Splicing: ADA: 0.03768

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.47

Publications

8 publications found

Variant links:

Genes affected

XPNPEP1 (HGNC:12822): (X-prolyl aminopeptidase 1) This gene encodes the cytosolic form of a metalloaminopeptidase that catalyzes the cleavage of the N-terminal amino acid adjacent to a proline residue. The gene product may play a role in degradation and maturation of tachykinins, neuropeptides, and peptide hormones. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Nov 2009]

XPNPEP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPNPEP1	NM_020383.4 link	c.1242-10T>G		intron_variant	Intron 13 of 20	ENST00000502935.6	NP_065116.3	Q9NQW7-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPNPEP1	ENST00000502935.6 link	c.1242-10T>G		intron_variant	Intron 13 of 20	1	NM_020383.4	ENSP00000421566.1		Q9NQW7-3

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30889

AN:

152060

Hom.:

3637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.216

AC:

54362

AN:

251432

AF XY:

0.228

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0827

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.179

AC:

261196

AN:

1461816

Hom.:

27998

Cov.:

AF XY:

0.186

AC XY:

135507

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.236

AC:

7902

AN:

33480

American (AMR)

AF:

0.0882

AC:

3943

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

4722

AN:

26136

East Asian (EAS)

AF:

0.320

AC:

12685

AN:

39700

South Asian (SAS)

AF:

0.425

AC:

36644

AN:

86254

European-Finnish (FIN)

AF:

0.283

AC:

15100

AN:

53420

Middle Eastern (MID)

AF:

0.225

AC:

1297

AN:

5764

European-Non Finnish (NFE)

AF:

0.150

AC:

167059

AN:

1111948

Other (OTH)

AF:

0.196

AC:

11844

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

11725

23450

35174

46899

58624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6144

12288

18432

24576

30720

<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:

0.203

AC:

30919

AN:

152180

Hom.:

3644

Cov.:

AF XY:

0.214

AC XY:

15896

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.235

AC:

9774

AN:

41520

American (AMR)

AF:

0.130

AC:

1986

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

634

AN:

3470

East Asian (EAS)

AF:

0.352

AC:

1820

AN:

5168

South Asian (SAS)

AF:

0.429

AC:

2068

AN:

4824

European-Finnish (FIN)

AF:

0.308

AC:

3259

AN:

10582

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10839

AN:

67992

Other (OTH)

AF:

0.181

AC:

383

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1222

2443

3665

4886

6108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.180

Hom.:

873

Bravo

AF:

0.185

Asia WGS

AF:

0.388

AC:

1349

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.038

dbscSNV1_RF

Benign

0.28

SpliceAI score (max)

0.020

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