Variant 1-146066405-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001302371.3(NBPF10):c.11301C>T(p.Phe3767=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 5 hom., cov: 11)

Exomes 𝑓: 0.0065 ( 27 hom. )

Failed GnomAD Quality Control

Consequence

NBPF10
NM_001302371.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.46

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.07).

BP6

Variant 1-146066405-G-A is Benign according to our data. Variant chr1-146066405-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639107.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.46 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00652 (4849/743280) while in subpopulation AFR AF= 0.0307 (615/20004). AF 95% confidence interval is 0.0287. There are 27 homozygotes in gnomad4_exome. There are 2560 alleles in male gnomad4_exome subpopulation. Median coverage is 10. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF10	NM_001302371.3 linkuse as main transcript	c.11301C>T	p.Phe3767=	synonymous_variant	90/90	ENST00000583866.9
NBPF10	NM_001039703.6 linkuse as main transcript	c.10794C>T	p.Phe3598=	synonymous_variant	86/86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF10	ENST00000583866.9 linkuse as main transcript	c.11301C>T	p.Phe3767=	synonymous_variant	90/90	5	NM_001302371.3	P1
NBPF10	ENST00000617010.2 linkuse as main transcript	c.3633C>T	p.Phe1211=	synonymous_variant	91/91	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1264

AN:

99898

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.00865

Gnomad AMR

AF:

0.00753

Gnomad ASJ

AF:

0.000371

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00554

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00694

AC:

1731

AN:

249484

Hom.:

AF XY:

0.00675

AC XY:

912

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.0282

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00796

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.00448

Gnomad OTH exome

AF:

0.00477

GnomAD4 exome

AF:

0.00652

AC:

4849

AN:

743280

Hom.:

Cov.:

AF XY:

0.00675

AC XY:

2560

AN XY:

379204

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.00455

Gnomad4 ASJ exome

AF:

0.000319

Gnomad4 EAS exome

AF:

0.000122

Gnomad4 SAS exome

AF:

0.00997

Gnomad4 FIN exome

AF:

0.0285

Gnomad4 NFE exome

AF:

0.00443

Gnomad4 OTH exome

AF:

0.00781

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0126

AC:

1263

AN:

99998

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

582

AN XY:

46082

show subpopulations

Gnomad4 AFR

AF:

0.0278

Gnomad4 AMR

AF:

0.00752

Gnomad4 ASJ

AF:

0.000371

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00666

Gnomad4 FIN

AF:

0.0239

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.0122

Alfa

AF:

0.0113

Hom.:

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

Dec 01, 2022

NBPF10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

3.5

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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