1-21470123-A-G

Variant names:

• chr1-21470123-A-G
• rs7537914
• NM_032264.6:c.344-509A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032264.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF3	NM_032264.6	MANE Select	c.344-509A>G		intron	N/A	NP_115640.1
	NBPF3	NM_001256416.4		c.344-509A>G		intron	N/A	NP_001243345.1
	NBPF3	NM_001330381.3		c.176-509A>G		intron	N/A	NP_001317310.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBPF3	ENST00000318249.10	TSL:1 MANE Select	c.344-509A>G		intron	N/A	ENSP00000316782.5
	NBPF3	ENST00000434838.6	TSL:5	n.*932-509A>G		intron	N/A	ENSP00000391865.2
	NBPF3	ENST00000342104.9	TSL:2	c.344-509A>G		intron	N/A	ENSP00000340336.5

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

African (AFR) AF: 0.481 AC: 19971 AN: 41482

American (AMR) AF: 0.763 AC: 11663 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2784 AN: 3470

East Asian (EAS) AF: 0.796 AC: 4124 AN: 5180

South Asian (SAS) AF: 0.872 AC: 4200 AN: 4814

European-Finnish (FIN) AF: 0.712 AC: 7532 AN: 10576

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49371 AN: 67978

Other (OTH) AF: 0.706 AC: 1490 AN: 2110

Alfa AF: 0.711 Hom.: 121666

Bravo AF: 0.661

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.29
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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: rs7537914; hg19: chr1-21796616;