rs1976403

Positions:

• chr1-21439960-A-C

Variant summary

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

The XM_047432037.1(NBPF3):​c.-140+3151A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,048 control chromosomes in the GnomAD database, including 8,848 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 0.33 (8848 hom., cov: 32)
• Consequence: NBPF3 XM_047432037.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBPF3	XM_047432037.1	c.-140+3151A>C		intron_variant			XP_047287993.1
NBPF3	XM_047432038.1	c.-140+2428A>C		intron_variant			XP_047287994.1
NBPF3	XM_047432039.1	c.-140+2428A>C		intron_variant			XP_047287995.1
		n.21439960A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49839 AN: 151930 Hom.: 8835 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.328 AC: 49885 AN: 152048 Hom.: 8848 Cov.: 32 AF XY: 0.330 AC XY: 24530 AN XY: 74300

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.321

Alfa AF: 0.374 Hom.: 3402

Bravo AF: 0.311

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	4.3
DANN	Benign	0.071

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1976403; hg19: chr1-21766453;