Variant 1-16576487-G-T details in Genebe, Genetics Data Aggregator

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

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]

NBPF1 links:

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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	Effect	Protein
NBPF1	NM_001405667.2 linkuse as main transcript	c.1905-6C>A	splice_region_variant, intron_variant	NP_001392596.1
NBPF1	NM_001405680.2 linkuse as main transcript	c.1905-6C>A	splice_region_variant, intron_variant	NP_001392609.1
NBPF1	NM_001405681.2 linkuse as main transcript	c.1905-6C>A	splice_region_variant, intron_variant	NP_001392610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBPF1	ENST00000430580.6 linkuse as main transcript	c.1905-6C>A		splice_region_variant, intron_variant		5		ENSP00000474456.1		Q3BBV0-2
NBPF1	ENST00000392963.5 linkuse as main transcript	n.*773-6C>A		splice_region_variant, intron_variant		5		ENSP00000473795.1		S4R2Z6

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

7773

AN:

109308

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

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 submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Mar 25, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over