Genetic Variant NXPE2:c.-47+20474A>G (chr11-114561234-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 XM_017017207.2(NXPE2):c.-47+20474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,982 control chromosomes in the GnomAD database, including 14,010 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 0.42 ( 14010 hom., cov: 32)

Consequence

NXPE2
XM_017017207.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.190

Publications

15 publications found

Variant links:

Genes affected

NXPE2 (HGNC:26331): (neurexophilin and PC-esterase domain family member 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NXPE2 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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXPE2	XM_017017207.2 link	c.-47+20474A>G		intron_variant	Intron 7 of 11		XP_016872696.1
NXPE2	XM_017017209.2 link	c.-47+20474A>G		intron_variant	Intron 6 of 10		XP_016872698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63329

AN:

151864

Hom.:

13987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.552

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.417

AC:

63405

AN:

151982

Hom.:

14010

Cov.:

AF XY:

0.420

AC XY:

31173

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.552

AC:

22881

AN:

41442

American (AMR)

AF:

0.359

AC:

5493

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1201

AN:

3466

East Asian (EAS)

AF:

0.664

AC:

3413

AN:

5142

South Asian (SAS)

AF:

0.329

AC:

1588

AN:

4822

European-Finnish (FIN)

AF:

0.391

AC:

4139

AN:

10574

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23611

AN:

67944

Other (OTH)

AF:

0.394

AC:

830

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1802

3603

5405

7206

9008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.359

Hom.:

13968

Bravo

AF:

0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.7

(source)

DANN

Benign

0.89

PhyloP100

-0.19

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over