Genetic Variant NBPF3:c.134-9113C>T (chr1-21459575-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0380

Publications

56 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:

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

PFN1P10 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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NBPF3	NM_032264.6	MANE Select	c.134-9113C>T	intron	N/A	NP_115640.1	Q9H094-1
NBPF3	NM_001256416.4		c.134-9113C>T	intron	N/A	NP_001243345.1	Q9H094-3
NBPF3	NM_001330381.3		c.-379+6145C>T	intron	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.134-9113C>T	intron	N/A	ENSP00000316782.5	Q9H094-1
NBPF3	ENST00000434838.6	TSL:5	n.*145-174C>T	intron	N/A	ENSP00000391865.2	X6RCV0
NBPF3	ENST00000912013.1		c.134-9113C>T	intron	N/A	ENSP00000582072.1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59126

AN:

151672

Hom.:

13594

Cov.:

show subpopulations

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.:

AF XY:

0.394

AC XY:

29206

AN XY:

74124

show subpopulations

African (AFR)

AF:

0.125

AC:

5180

AN:

41422

American (AMR)

AF:

0.486

AC:

7414

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1698

AN:

3470

East Asian (EAS)

AF:

0.557

AC:

2885

AN:

5176

South Asian (SAS)

AF:

0.448

AC:

2146

AN:

4794

European-Finnish (FIN)

AF:

0.476

AC:

4983

AN:

10466

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33276

AN:

67900

Other (OTH)

AF:

0.437

AC:

921

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1593

3186

4779

6372

7965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.457

Hom.:

55800

Bravo

AF:

0.377

Asia WGS

AF:

0.436

AC:

1517

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.4

(source)

DANN

Benign

0.28

PhyloP100

-0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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