1-21459575-C-T

Variant names:

• chr1-21459575-C-T
• rs4654748
• NM_032264.6:c.134-9113C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032264.6(NBPF3):​c.134-9113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,790 control chromosomes in the GnomAD database, including 13,594 homozygotes. 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 0.39 (13594 hom., cov: 31)
• Consequence: NBPF3 NM_032264.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

Genes affected

NBPF3 (HGNC:25076): (NBPF member 3) 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. DUF1220 copy number variations in 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, Feb 2013]

PFN1P10 (HGNC:42985): (profilin 1 pseudogene 10)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBPF3	NM_032264.6	c.134-9113C>T		intron_variant	Intron 2 of 14	ENST00000318249.10	NP_115640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBPF3	ENST00000318249.10	c.134-9113C>T		intron_variant	Intron 2 of 14	1	NM_032264.6	ENSP00000316782.5
NBPF3	ENST00000434838.6	n.*145-174C>T		intron_variant	Intron 3 of 18	5		ENSP00000391865.2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59126 AN: 151672 Hom.: 13594 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.439

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59119 AN: 151790 Hom.: 13594 Cov.: 31 AF XY: 0.394 AC XY: 29206 AN XY: 74124

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.437

Alfa AF: 0.471 Hom.: 19540

Bravo AF: 0.377

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.28

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: rs4654748; hg19: chr1-21786068;