1-149072907-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_001388367.1(NBPF9):c.1117C>T(p.Gln373Ter) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_001388367.1 Downstream stopcodon found after 11 codons.
• 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 GnomAd at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF9	NM_001388367.1	c.1117C>T	p.Gln373Ter	stop_gained	14/30	ENST00000698832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF9	ENST00000698832.1	c.1117C>T	p.Gln373Ter	stop_gained	14/30		NM_001388367.1	P1

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 578 AN: 151334 Hom.: 15 Cov.: 29

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.: 31 AF XY: 0.00326 AC XY: 441 AN XY: 135388

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.: 32 AF XY: 0.00550 AC XY: 3985 AN XY: 724364

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.: 15 Cov.: 29 AF XY: 0.00391 AC XY: 289 AN XY: 73964

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.: 9

Bravo AF: 0.00387

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

NBPF9: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
Cadd	Pathogenic	34
Dann	Uncertain	0.99
Eigen	Uncertain	0.21
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.15	N
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

Other links and lift over

dbSNP: rs201767679; hg19: chr1-148337507; COSMIC: COSV99913804;