Variant NM_001388367.1:c.1117C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001388367.1(NBPF9):c.1117C>T(p.Gln373*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,607,260 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0038 ( 15 hom., cov: 29)

Exomes 𝑓: 0.0057 ( 315 hom. )

Consequence

NBPF9
NM_001388367.1 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.73

Variant links:

Genes affected

NBPF9 (HGNC:31991): (NBPF member 9) 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]

NBPF9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-149072907-G-A is Benign according to our data. Variant chr1-149072907-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639062.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF9	NM_001388367.1 link	c.1117C>T	p.Gln373*	stop_gained	Exon 14 of 30	ENST00000698832.1	NP_001375296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF9	ENST00000698832.1 link	c.1117C>T	p.Gln373*	stop_gained	Exon 14 of 30		NM_001388367.1	ENSP00000513968.1		P0DPF3-1

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

578

AN:

151334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.0306

Gnomad AMR

AF:

0.00330

Gnomad ASJ

AF:

0.00435

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00343

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00572

Gnomad OTH

AF:

0.00531

GnomAD3 exomes

AF:

0.00350

AC:

874

AN:

249660

Hom.:

AF XY:

0.00326

AC XY:

441

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00519

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.00540

Gnomad OTH exome

AF:

0.00346

GnomAD4 exome

AF:

0.00570

AC:

8301

AN:

1455808

Hom.:

315

Cov.:

AF XY:

0.00550

AC XY:

3985

AN XY:

724364

show subpopulations

Gnomad4 AFR exome

AF:

0.000898

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00499

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00276

Gnomad4 NFE exome

AF:

0.00681

Gnomad4 OTH exome

AF:

0.00513

GnomAD4 genome

AF:

0.00382

AC:

578

AN:

151452

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

289

AN XY:

73964

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00329

Gnomad4 ASJ

AF:

0.00435

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00343

Gnomad4 NFE

AF:

0.00572

Gnomad4 OTH

AF:

0.00525

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.00387

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NBPF9: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.21

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.15

Vest4

0.16

GERP RS

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