dbSNP rs3024979: NAB2:c.1469-102A>T (chr12-57094510-A-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_005967.4(NAB2):c.1469-102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 913,236 control chromosomes in the GnomAD database, including 3,794 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 0.070 ( 536 hom., cov: 32)

Exomes 𝑓: 0.087 ( 3258 hom. )

Consequence

NAB2
NM_005967.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.393

Publications

13 publications found

Variant links:

COSMIC-nc: COSV100272550

Genes affected

NAB2 (HGNC:7627): (NGFI-A binding protein 2) This gene encodes a member of the family of NGFI-A binding (NAB) proteins, which function in the nucleus to repress transcription induced by some members of the EGR (early growth response) family of transactivators. NAB proteins can homo- or hetero-multimerize with other EGR or NAB proteins through a conserved N-terminal domain, and repress transcription through two partially redundant C-terminal domains. Transcriptional repression by the encoded protein is mediated in part by interactions with the nucleosome remodeling and deactylase (NuRD) complex. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

NAB2 links:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAB2	NM_005967.4 link	c.1469-102A>T		intron_variant	Intron 6 of 6	ENST00000300131.8	NP_005958.1	Q15742-1
NAB2	NM_001330305.2 link	c.1277-102A>T		intron_variant	Intron 5 of 5		NP_001317234.1	Q15742-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAB2	ENST00000300131.8 link	c.1469-102A>T		intron_variant	Intron 6 of 6	1	NM_005967.4	ENSP00000300131.3		Q15742-1
NAB2	ENST00000342556.6 link	c.1277-102A>T		intron_variant	Intron 5 of 5	5		ENSP00000341491.6		Q15742-3

Frequencies

GnomAD3 genomes

AF:

0.0705

AC:

10717

AN:

152012

Hom.:

535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0794

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0336

Gnomad FIN

AF:

0.0688

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0869

AC:

66133

AN:

761106

Hom.:

3258

AF XY:

0.0851

AC XY:

33872

AN XY:

398092

show subpopulations

African (AFR)

AF:

0.0195

AC:

380

AN:

19484

American (AMR)

AF:

0.0689

AC:

2397

AN:

34770

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

2827

AN:

21092

East Asian (EAS)

AF:

0.000182

AC:

AN:

33006

South Asian (SAS)

AF:

0.0337

AC:

2237

AN:

66396

European-Finnish (FIN)

AF:

0.0767

AC:

3014

AN:

39302

Middle Eastern (MID)

AF:

0.155

AC:

697

AN:

4492

European-Non Finnish (NFE)

AF:

0.101

AC:

51039

AN:

505392

Other (OTH)

AF:

0.0951

AC:

3536

AN:

37172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3404

6808

10212

13616

17020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1080

2160

3240

4320

5400

<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:

0.0704

AC:

10714

AN:

152130

Hom.:

536

Cov.:

AF XY:

0.0682

AC XY:

5068

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0180

AC:

746

AN:

41514

American (AMR)

AF:

0.0793

AC:

1212

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

482

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5170

South Asian (SAS)

AF:

0.0338

AC:

163

AN:

4818

European-Finnish (FIN)

AF:

0.0688

AC:

728

AN:

10586

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7015

AN:

67966

Other (OTH)

AF:

0.102

AC:

215

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

503

1006

1510

2013

2516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0857

Hom.:

Bravo

AF:

0.0718

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

(source)

DANN

Benign

0.52

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over