chr1-16576487-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001405667.2(NBPF1):​c.1905-6C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 109,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.071 ( 0 hom., cov: 73)
Exomes 𝑓: 0.014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NBPF1
NM_001405667.2 splice_region, intron

Scores

2

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.0910
Variant links:
Genes affected
NBPF1 (HGNC:26088): (NBPF member 1) 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. [provided by RefSeq, Apr 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NBPF1NM_001405667.2 linkuse as main transcriptc.1905-6C>A splice_region_variant, intron_variant NP_001392596.1
NBPF1NM_001405680.2 linkuse as main transcriptc.1905-6C>A splice_region_variant, intron_variant NP_001392609.1
NBPF1NM_001405681.2 linkuse as main transcriptc.1905-6C>A splice_region_variant, intron_variant NP_001392610.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NBPF1ENST00000430580.6 linkuse as main transcriptc.1905-6C>A splice_region_variant, intron_variant 5 ENSP00000474456.1 Q3BBV0-2
NBPF1ENST00000392963.5 linkuse as main transcriptn.*773-6C>A splice_region_variant, intron_variant 5 ENSP00000473795.1 S4R2Z6

Frequencies

GnomAD3 genomes
AF:
0.0711
AC:
7773
AN:
109308
Hom.:
0
Cov.:
73
show subpopulations
Gnomad AFR
AF:
0.0580
Gnomad AMI
AF:
0.0554
Gnomad AMR
AF:
0.0928
Gnomad ASJ
AF:
0.0470
Gnomad EAS
AF:
0.324
Gnomad SAS
AF:
0.0601
Gnomad FIN
AF:
0.0897
Gnomad MID
AF:
0.0982
Gnomad NFE
AF:
0.0573
Gnomad OTH
AF:
0.0685
GnomAD3 exomes
AF:
0.0386
AC:
7327
AN:
189788
Hom.:
0
AF XY:
0.0363
AC XY:
3791
AN XY:
104356
show subpopulations
Gnomad AFR exome
AF:
0.0263
Gnomad AMR exome
AF:
0.0456
Gnomad ASJ exome
AF:
0.0248
Gnomad EAS exome
AF:
0.227
Gnomad SAS exome
AF:
0.0210
Gnomad FIN exome
AF:
0.0238
Gnomad NFE exome
AF:
0.0241
Gnomad OTH exome
AF:
0.0442
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0138
AC:
17073
AN:
1233606
Hom.:
0
Cov.:
51
AF XY:
0.0139
AC XY:
8513
AN XY:
614546
show subpopulations
Gnomad4 AFR exome
AF:
0.0140
Gnomad4 AMR exome
AF:
0.0209
Gnomad4 ASJ exome
AF:
0.0139
Gnomad4 EAS exome
AF:
0.202
Gnomad4 SAS exome
AF:
0.00941
Gnomad4 FIN exome
AF:
0.0241
Gnomad4 NFE exome
AF:
0.00818
Gnomad4 OTH exome
AF:
0.0218
GnomAD4 genome
AF:
0.0711
AC:
7776
AN:
109406
Hom.:
0
Cov.:
73
AF XY:
0.0730
AC XY:
3907
AN XY:
53498
show subpopulations
Gnomad4 AFR
AF:
0.0579
Gnomad4 AMR
AF:
0.0929
Gnomad4 ASJ
AF:
0.0470
Gnomad4 EAS
AF:
0.325
Gnomad4 SAS
AF:
0.0595
Gnomad4 FIN
AF:
0.0897
Gnomad4 NFE
AF:
0.0573
Gnomad4 OTH
AF:
0.0691
Alfa
AF:
0.110
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of PhiladelphiaMar 25, 2015- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
1.7
DANN
Benign
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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: rs3896430; hg19: chr1-16902982; COSMIC: COSV55328195; API