chr1-19656882-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005380.8(NBL1):c.299C>T(p.Pro100Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,611,438 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

NBL1
NM_005380.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.26

Publications

3 publications found

Variant links:

Genes affected

NBL1 (HGNC:7650): (NBL1, DAN family BMP antagonist) This gene product is the founding member of the evolutionarily conserved CAN (Cerberus and DAN) family of proteins, which contain a domain resembling the CTCK (C-terminal cystine knot-like) motif found in a number of signaling molecules. These proteins are secreted, and act as BMP (bone morphogenetic protein) antagonists by binding to BMPs and preventing them from interacting with their receptors. They may thus play an important role during growth and development. Alternatively spliced transcript variants have been identified for this gene. Read-through transcripts between this locus and the upstream mitochondrial inner membrane organizing system 1 gene (GeneID 440574) have been observed. [provided by RefSeq, May 2013]

NBL1 links:

MICOS10-NBL1 (HGNC:48338): (MICOS10-NBL1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring chromosome 1 open reading frame 151 (GeneID 440574) and neuroblastoma suppressor of tumorigenicity 1 (GeneID 4681) genes on chromosome 1. The read-through transcripts produce at least two proteins, each of which share identity with proteins translated from the downstream neuroblastoma suppressor of tumorigenicity 1 locus. [provided by RefSeq, Feb 2011]

MICOS10-NBL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005380.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBL1	NM_005380.8	MANE Select	c.299C>T	p.Pro100Leu	missense	Exon 4 of 4	NP_005371.2	P41271-1
NBL1	NM_182744.4		c.404C>T	p.Pro135Leu	missense	Exon 4 of 4	NP_877421.2	P41271-2
NBL1	NM_001204086.3		c.401C>T	p.Pro134Leu	missense	Exon 4 of 4	NP_001191015.1	A0A087WTY6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NBL1	ENST00000375136.8	TSL:1 MANE Select	c.299C>T	p.Pro100Leu	missense	Exon 4 of 4	ENSP00000364278.4	P41271-1
NBL1	ENST00000615215.4	TSL:1	c.401C>T	p.Pro134Leu	missense	Exon 4 of 4	ENSP00000478223.1	A0A087WTY6
NBL1	ENST00000618761.4	TSL:1	c.299C>T	p.Pro100Leu	missense	Exon 4 of 4	ENSP00000483061.1	P41271-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

245378

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1459362

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.000112

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26020

East Asian (EAS)

AF:

0.000151

AC:

AN:

39606

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

1110314

Other (OTH)

AF:

0.0000830

AC:

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41386

American (AMR)

AF:

0.000590

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000152

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.0063

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.4

PhyloP100

7.3

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.25

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.63

MVP

0.89

MPC

1.3

ClinPred

0.95

GERP RS

3.2

Varity_R

0.45

gMVP

0.87

Mutation Taster

=45/55

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over