15-73633441-A-C

Variant summary

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

The ENST00000351217.10(NPTN):​c.-226T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 397,134 control chromosomes in the GnomAD database, including 51,528 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 0.49 ( 18531 hom., cov: 32)
Exomes 𝑓: 0.52 ( 32997 hom. )

Consequence

NPTN
ENST00000351217.10 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.501

Publications

7 publications found
Variant links:
Genes affected
NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]

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=-0.68).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPTNNM_012428.4 linkc.-226T>G upstream_gene_variant ENST00000345330.9 NP_036560.1 Q9Y639-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPTNENST00000345330.9 linkc.-226T>G upstream_gene_variant 1 NM_012428.4 ENSP00000290401.4 Q9Y639-2

Frequencies

GnomAD3 genomes
AF:
0.490
AC:
74446
AN:
151802
Hom.:
18518
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.422
Gnomad AMI
AF:
0.597
Gnomad AMR
AF:
0.527
Gnomad ASJ
AF:
0.455
Gnomad EAS
AF:
0.531
Gnomad SAS
AF:
0.447
Gnomad FIN
AF:
0.528
Gnomad MID
AF:
0.437
Gnomad NFE
AF:
0.519
Gnomad OTH
AF:
0.480
GnomAD4 exome
AF:
0.516
AC:
126459
AN:
245214
Hom.:
32997
Cov.:
3
AF XY:
0.514
AC XY:
65006
AN XY:
126554
show subpopulations
African (AFR)
AF:
0.424
AC:
2823
AN:
6662
American (AMR)
AF:
0.529
AC:
3607
AN:
6824
Ashkenazi Jewish (ASJ)
AF:
0.452
AC:
3998
AN:
8842
East Asian (EAS)
AF:
0.595
AC:
12874
AN:
21646
South Asian (SAS)
AF:
0.432
AC:
3745
AN:
8662
European-Finnish (FIN)
AF:
0.535
AC:
11008
AN:
20578
Middle Eastern (MID)
AF:
0.476
AC:
579
AN:
1216
European-Non Finnish (NFE)
AF:
0.516
AC:
79930
AN:
155020
Other (OTH)
AF:
0.501
AC:
7895
AN:
15764
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
2822
5643
8465
11286
14108
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
350
700
1050
1400
1750
<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:
0.490
AC:
74515
AN:
151920
Hom.:
18531
Cov.:
32
AF XY:
0.492
AC XY:
36534
AN XY:
74244
show subpopulations
African (AFR)
AF:
0.422
AC:
17506
AN:
41462
American (AMR)
AF:
0.528
AC:
8066
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.455
AC:
1580
AN:
3470
East Asian (EAS)
AF:
0.532
AC:
2708
AN:
5092
South Asian (SAS)
AF:
0.446
AC:
2147
AN:
4816
European-Finnish (FIN)
AF:
0.528
AC:
5591
AN:
10580
Middle Eastern (MID)
AF:
0.449
AC:
132
AN:
294
European-Non Finnish (NFE)
AF:
0.519
AC:
35231
AN:
67908
Other (OTH)
AF:
0.480
AC:
1012
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1980
3960
5939
7919
9899
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
666
1332
1998
2664
3330
<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:
0.353
Hom.:
912
Bravo
AF:
0.489
Asia WGS
AF:
0.465
AC:
1621
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
14
DANN
Benign
0.86
PhyloP100
-0.50
PromoterAI
-0.022
Neutral
Mutation Taster
=300/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs3743500; hg19: chr15-73925782; COSMIC: COSV54740320; COSMIC: COSV54740320; API