1-149079092-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001388367.1(NBPF9):c.408G>A(p.Pro136=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000989 in 133,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00099 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0037 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.32

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 1-149079092-C-T is Benign according to our data. Variant chr1-149079092-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639058.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF9	NM_001388367.1	c.408G>A	p.Pro136=	synonymous_variant	9/30	ENST00000698832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF9	ENST00000698832.1	c.408G>A	p.Pro136=	synonymous_variant	9/30		NM_001388367.1	P1

Frequencies

GnomAD3 genomes AF: 0.000990 AC: 132 AN: 133354 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000522

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00293

Gnomad SAS AF: 0.00801

Gnomad FIN AF: 0.000534

Gnomad MID AF: 0.00327

Gnomad NFE AF: 0.000422

Gnomad OTH AF: 0.00231

GnomAD3 exomes AF: 0.000117 AC: 29 AN: 247314 Hom.: 0 AF XY: 0.000111 AC XY: 15 AN XY: 134634

Gnomad AFR exome AF: 0.000273

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000896

Gnomad OTH exome AF: 0.000166

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00368 AC: 4113 AN: 1116156 Hom.: 7 Cov.: 17 AF XY: 0.00514 AC XY: 2907 AN XY: 565212

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.00108

Gnomad4 ASJ exome AF: 0.000971

Gnomad4 EAS exome AF: 0.00714

Gnomad4 SAS exome AF: 0.00741

Gnomad4 FIN exome AF: 0.0115

Gnomad4 NFE exome AF: 0.00292

Gnomad4 OTH exome AF: 0.00486

GnomAD4 genome AF: 0.000989 AC: 132 AN: 133466 Hom.: 0 Cov.: 24 AF XY: 0.00118 AC XY: 76 AN XY: 64490

Gnomad4 AFR AF: 0.00131

Gnomad4 AMR AF: 0.000521

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00294

Gnomad4 SAS AF: 0.00802

Gnomad4 FIN AF: 0.000534

Gnomad4 NFE AF: 0.000422

Gnomad4 OTH AF: 0.00229

Alfa AF: 0.000843 Hom.: 0

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, 2022

NBPF9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	7.2
Dann	Benign	0.59

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: rs782691322; hg19: chr1-148343679; COSMIC: COSV64994964; COSMIC: COSV64994964;