1-149072882-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001388367.1(NBPF9):c.1142G>A(p.Arg381Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000016 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.054292142).
• BP6: Variant 1-149072882-C-T is Benign according to our data. Variant chr1-149072882-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF9	NM_001388367.1	c.1142G>A	p.Arg381Lys	missense_variant	14/30	ENST00000698832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF9	ENST00000698832.1	c.1142G>A	p.Arg381Lys	missense_variant	14/30		NM_001388367.1	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 9 AN: 149274 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.0000973

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000903

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00144 AC: 356 AN: 246958 Hom.: 25 AF XY: 0.00149 AC XY: 200 AN XY: 134044

Gnomad AFR exome AF: 0.000834

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.00122

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000889

Gnomad FIN exome AF: 0.000373

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.00268

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000158 AC: 23 AN: 1454114 Hom.: 4 Cov.: 32 AF XY: 0.0000207 AC XY: 15 AN XY: 723514

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000697

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000903

Gnomad4 OTH exome AF: 0.0000500

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000602 AC: 9 AN: 149390 Hom.: 0 Cov.: 29 AF XY: 0.0000685 AC XY: 5 AN XY: 72960

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000295

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.0000973

Gnomad4 NFE AF: 0.0000903

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00743 Hom.: 4

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
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	0.34
Dann	Benign	0.63
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0031	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.054	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.64	T
Sift4G	Benign	0.46	T;T;T;T;T;T;T;T
Vest4		0.31
MutPred		0.30		Gain of ubiquitination at R381 (P = 0.0109);Gain of ubiquitination at R381 (P = 0.0109);Gain of ubiquitination at R381 (P = 0.0109);Gain of ubiquitination at R381 (P = 0.0109);Gain of ubiquitination at R381 (P = 0.0109);Gain of ubiquitination at R381 (P = 0.0109);.;Gain of ubiquitination at R381 (P = 0.0109);
MVP		0.32
ClinPred		0.028	T
GERP RS		-0.83
Varity_R		0.030

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: rs781861714; hg19: chr1-148337482;