rs4068622

Variant names:

• chr1-149082405-T-C
• rs4067685
• NM_001388367.1:c.-169A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001388367.1(NBPF9):​c.-169A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBPF9 NM_001388367.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735
• Publications: 1 publications found

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]

ENSG00000301832 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF9	NM_001388367.1	c.-169A>G		5_prime_UTR_variant	Exon 6 of 30	ENST00000698832.1	NP_001375296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF9	ENST00000698832.1	c.-169A>G		5_prime_UTR_variant	Exon 6 of 30		NM_001388367.1	ENSP00000513968.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000107 AC: 1 AN: 931010 Hom.: 0 Cov.: 13 AF XY: 0.00000211 AC XY: 1 AN XY: 474096

African (AFR) AF: 0.00 AC: 0 AN: 19840

American (AMR) AF: 0.00 AC: 0 AN: 26692

Ashkenazi Jewish (ASJ) AF: 0.0000490 AC: 1 AN: 20414

East Asian (EAS) AF: 0.00 AC: 0 AN: 31852

South Asian (SAS) AF: 0.00 AC: 0 AN: 62094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3072

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 692460

Other (OTH) AF: 0.00 AC: 0 AN: 41774

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.17
PhyloP100		-0.73
PromoterAI		0.0028	Neutral

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

Other links and lift over

dbSNP: rs4067685; hg19: chr1-148347023;