1-21470123-A-G

Position:

• chr1-21470123-A-G

Variant summary

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

The NM_032264.6(NBPF3):​c.344-509A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,088 control chromosomes in the GnomAD database, including 35,356 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 0.67 (35356 hom., cov: 31)
• Consequence: NBPF3 NM_032264.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NBPF3	NM_032264.6	c.344-509A>G		intron_variant		ENST00000318249.10	NP_115640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBPF3	ENST00000318249.10	c.344-509A>G		intron_variant		1	NM_032264.6	ENSP00000316782	P2

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101893 AN: 151970 Hom.: 35348 Cov.: 31

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.670 AC: 101949 AN: 152088 Hom.: 35356 Cov.: 31 AF XY: 0.676 AC XY: 50277 AN XY: 74346

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.706

Alfa AF: 0.725 Hom.: 78874

Bravo AF: 0.661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.29

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: rs7537914; hg19: chr1-21796616;