dbSNP rs1976403: NBPF3:c.-140+3151A>C (chr1-21439960-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.27

Publications

37 publications found

Variant links:

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]

NBPF3 links:

ENSG00000295832 (HGNC:):

ENSG00000295832 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000318249.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NBPF3	NM_032264.6	MANE Select	c.-528A>C	upstream_gene	N/A	NP_115640.1	Q9H094-1
NBPF3	NM_001256416.4		c.-528A>C	upstream_gene	N/A	NP_001243345.1	Q9H094-3
NBPF3	NM_001330381.3		c.-1097A>C	upstream_gene	N/A	NP_001317310.1	Q9H094-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NBPF3	ENST00000318249.10	TSL:1 MANE Select	c.-528A>C	upstream_gene	N/A	ENSP00000316782.5	Q9H094-1
NBPF3	ENST00000485941.2	TSL:1	n.-186A>C	upstream_gene	N/A
NBPF3	ENST00000912013.1		c.-365A>C	upstream_gene	N/A	ENSP00000582072.1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49839

AN:

151930

Hom.:

8835

Cov.:

show subpopulations

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.:

AF XY:

0.330

AC XY:

24530

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.197

AC:

8178

AN:

41500

American (AMR)

AF:

0.294

AC:

4492

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1276

AN:

3468

East Asian (EAS)

AF:

0.254

AC:

1307

AN:

5136

South Asian (SAS)

AF:

0.463

AC:

2233

AN:

4820

European-Finnish (FIN)

AF:

0.416

AC:

4398

AN:

10566

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.395

AC:

26819

AN:

67956

Other (OTH)

AF:

0.321

AC:

678

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1695

3389

5084

6778

8473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.368

Hom.:

18294

Bravo

AF:

0.311

Asia WGS

AF:

0.383

AC:

1333

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

4.3

(source)

DANN

Benign

0.071

PhyloP100

-3.3

PromoterAI

0.071

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over