1-149063676-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_Moderate BP7

The NM_001388367.1(NBPF9):c.1983C>T(p.Tyr661=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 18)
  • Exomes 𝑓: 0.00025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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 -3 ACMG points.

• BP6: Variant 1-149063676-G-A is Benign according to our data. Variant chr1-149063676-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639064.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.038 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF9	NM_001388367.1	c.1983C>T	p.Tyr661=	synonymous_variant	20/30	ENST00000698832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF9	ENST00000698832.1	c.1983C>T	p.Tyr661=	synonymous_variant	20/30		NM_001388367.1	P1

Frequencies

GnomAD3 genomes AF: 0.000212 AC: 28 AN: 132132 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.000179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000853

Gnomad SAS AF: 0.000284

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000238

Gnomad OTH AF: 0.000575

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000249 AC: 121 AN: 486228 Hom.: 0 Cov.: 0 AF XY: 0.000292 AC XY: 76 AN XY: 260348

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.000126

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000531

Gnomad4 SAS exome AF: 0.000384

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000253

Gnomad4 OTH exome AF: 0.000290

GnomAD4 genome AF: 0.000212 AC: 28 AN: 132216 Hom.: 0 Cov.: 18 AF XY: 0.000142 AC XY: 9 AN XY: 63192

Gnomad4 AFR AF: 0.000178

Gnomad4 AMR AF: 0.000152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000856

Gnomad4 SAS AF: 0.000284

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000238

Gnomad4 OTH AF: 0.000570

Alfa AF: 0.00483 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

Nov 01, 2022

NBPF9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.080
Cadd	Benign	3.1
Dann	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75211907; hg19: chr1-144823942;