1-146126300-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001302371.3(NBPF10):​c.1962G>A​(p.Gln654Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,585,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

NBPF10
NM_001302371.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.825
Variant links:
Genes affected
NBPF10 (HGNC:31992): (NBPF member 10) This gene is a member of the neuroblastoma breakpoint family (NBPF) which consists of dozens of recently duplicated genes primarily located in segmental duplications on human chromosome 1. This gene family has experienced its greatest expansion within the human lineage and has expanded, to a lesser extent, among primates in general. Members of this gene family are characterized by tandemly repeated copies of DUF1220 protein domains. Gene copy number variations in the human chromosomal region 1q21.1, where most DUF1220 domains are located, have been implicated in a number of developmental and neurogenetic diseases such as microcephaly, macrocephaly, autism, schizophrenia, cognitive disability, congenital heart disease, neuroblastoma, and congenital kidney and urinary tract anomalies. Altered expression of some gene family members is associated with several types of cancer. This gene family contains numerous pseudogenes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BP6
Variant 1-146126300-C-T is Benign according to our data. Variant chr1-146126300-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639091.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.825 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NBPF10NM_001302371.3 linkc.1962G>A p.Gln654Gln synonymous_variant Exon 14 of 90 ENST00000583866.9 NP_001289300.1 Q6P3W6
NBPF10NM_001039703.6 linkc.1962G>A p.Gln654Gln synonymous_variant Exon 14 of 86 NP_001034792.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NBPF10ENST00000583866.9 linkc.1962G>A p.Gln654Gln synonymous_variant Exon 14 of 90 5 NM_001302371.3 ENSP00000463957.6 Q6P3W6
NBPF10ENST00000617010.2 linkc.-5914G>A 5_prime_UTR_variant Exon 14 of 91 5 ENSP00000479344.2 A0A087WVC7
NBPF10ENST00000612520.2 linkc.1853+728G>A intron_variant Intron 18 of 20 5 ENSP00000483006.2 A0A087X002

Frequencies

GnomAD3 genomes
AF:
0.0000330
AC:
5
AN:
151706
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.0000127
AC:
3
AN:
236266
Hom.:
0
AF XY:
0.0000155
AC XY:
2
AN XY:
128876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000559
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000195
AC:
28
AN:
1433300
Hom.:
0
Cov.:
28
AF XY:
0.0000210
AC XY:
15
AN XY:
714738
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000818
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000175
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
151822
Hom.:
0
Cov.:
30
AF XY:
0.0000269
AC XY:
2
AN XY:
74222
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.000475
Bravo
AF:
0.0000340

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Apr 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

NBPF10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.23
DANN
Benign
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782443316; hg19: chr1-145311894; API