1-149063766-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001388367.1(NBPF9):c.1893C>A(p.Val631=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 18)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: NBPF9 NM_001388367.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-149063766-G-T is Benign according to our data. Variant chr1-149063766-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.097 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF9	NM_001388367.1	c.1893C>A	p.Val631=	synonymous_variant	20/30	ENST00000698832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF9	ENST00000698832.1	c.1893C>A	p.Val631=	synonymous_variant	20/30		NM_001388367.1	P1

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 191 AN: 136464 Hom.: 2 Cov.: 18

Gnomad AFR AF: 0.000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000820

Gnomad ASJ AF: 0.000303

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000213

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.00281

GnomAD4 exome AF: 0.00173 AC: 820 AN: 474594 Hom.: 1 Cov.: 0 AF XY: 0.00175 AC XY: 442 AN XY: 253082

Gnomad4 AFR exome AF: 0.000235

Gnomad4 AMR exome AF: 0.00205

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00107

Gnomad4 NFE exome AF: 0.00242

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00140 AC: 191 AN: 136552 Hom.: 2 Cov.: 18 AF XY: 0.00122 AC XY: 80 AN XY: 65550

Gnomad4 AFR AF: 0.000255

Gnomad4 AMR AF: 0.000819

Gnomad4 ASJ AF: 0.000303

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000213

Gnomad4 NFE AF: 0.00251

Gnomad4 OTH AF: 0.00278

Alfa AF: 0.00168 Hom.: 1

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

May 01, 2022

NBPF9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.68
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs782474996; hg19: chr1-144823852;