Variant 1-146125486-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001302371.3(NBPF10):c.2057A>T(p.Asp686Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 2 hom., cov: 9)

Exomes 𝑓: 0.00067 ( 3 hom. )

Consequence

NBPF10
NM_001302371.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44

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]

NBPF10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030658394).

BP6

Variant 1-146125486-T-A is Benign according to our data. Variant chr1-146125486-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639093.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF10	NM_001302371.3 linkuse as main transcript	c.2057A>T	p.Asp686Val	missense_variant	15/90	ENST00000583866.9
NBPF10	NM_001039703.6 linkuse as main transcript	c.2057A>T	p.Asp686Val	missense_variant	15/86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NBPF10	ENST00000583866.9 linkuse as main transcript	c.2057A>T	p.Asp686Val	missense_variant	15/90	5	NM_001302371.3	P1
NBPF10	ENST00000617010.2 linkuse as main transcript	c.-5819A>T		5_prime_UTR_variant	15/91	5
NBPF10	ENST00000612520.2 linkuse as main transcript	c.1853+1542A>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000626

AC:

AN:

71870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000626

Gnomad AMI

AF:

0.00417

Gnomad AMR

AF:

0.000506

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000460

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000575

AC:

AN:

52142

Hom.:

AF XY:

0.000498

AC XY:

AN XY:

26098

show subpopulations

Gnomad AFR exome

AF:

0.000395

Gnomad AMR exome

AF:

0.000949

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000522

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000746

Gnomad OTH exome

AF:

0.000552

GnomAD4 exome

AF:

0.000669

AC:

260

AN:

388812

Hom.:

Cov.:

AF XY:

0.000648

AC XY:

138

AN XY:

212966

show subpopulations

Gnomad4 AFR exome

AF:

0.000314

Gnomad4 AMR exome

AF:

0.000993

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000520

Gnomad4 FIN exome

AF:

0.000218

Gnomad4 NFE exome

AF:

0.000842

Gnomad4 OTH exome

AF:

0.000708

GnomAD4 genome

AF:

0.000626

AC:

AN:

71902

Hom.:

Cov.:

AF XY:

0.000597

AC XY:

AN XY:

33482

show subpopulations

Gnomad4 AFR

AF:

0.0000624

Gnomad4 AMR

AF:

0.000506

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000459

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000367

Hom.:

Bravo

AF:

0.000706

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

NBPF10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

LIST_S2

Benign

0.85

MetaRNN

Benign

0.031

Sift4G

Pathogenic

0.0

Vest4

0.15

gMVP

0.039

Splicing

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