rs4068622

Positions:

• chr1-149082405-T-A
• chr1-149082405-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001388367.1(NBPF9):​c.-169A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBPF9	NM_001388367.1	c.-169A>T		5_prime_UTR_variant	6/30	ENST00000698832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBPF9	ENST00000698832.1	c.-169A>T		5_prime_UTR_variant	6/30		NM_001388367.1	P1
NBPF9	ENST00000615421.4	c.-164A>T		5_prime_UTR_variant	5/29	5		P1
NBPF9	ENST00000698196.1	c.-169A>T		5_prime_UTR_variant	8/32			P1
NBPF9	ENST00000621645.4	c.-35-231A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148126 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000430 AC: 4 AN: 931000 Hom.: 0 Cov.: 13 AF XY: 0.00000633 AC XY: 3 AN XY: 474092

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000375

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000314

Gnomad4 SAS exome AF: 0.0000322

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000675 AC: 1 AN: 148126 Hom.: 0 Cov.: 23 AF XY: 0.0000139 AC XY: 1 AN XY: 72058

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000843 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.16

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: rs4067685; hg19: chr1-148347023;