Variant 12-57091672-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005967.4(NAB2):c.631C>T(p.Pro211Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0118 in 1,611,668 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 146 hom. )

Consequence

NAB2
NM_005967.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.79

Variant links:

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051959455).

BP6

Variant 12-57091672-C-T is Benign according to our data. Variant chr12-57091672-C-T is described in ClinVar as [Benign]. Clinvar id is 779440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1262 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAB2	NM_005967.4 link	c.631C>T	p.Pro211Ser	missense_variant	2/7	ENST00000300131.8	NP_005958.1	Q15742-1
NAB2	NM_001330305.2 link	c.631C>T	p.Pro211Ser	missense_variant	2/6		NP_001317234.1	Q15742-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NAB2	ENST00000300131.8 link	c.631C>T	p.Pro211Ser	missense_variant	2/7	1	NM_005967.4	ENSP00000300131.3	Q15742-1
NAB2	ENST00000342556.6 link	c.631C>T	p.Pro211Ser	missense_variant	2/6	5		ENSP00000341491.6	Q15742-3
NAB2	ENST00000554718.1 link	n.647C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.00830

AC:

1262

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0132

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00903

AC:

2203

AN:

243854

Hom.:

AF XY:

0.00929

AC XY:

1236

AN XY:

133042

show subpopulations

Gnomad AFR exome

AF:

0.00225

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.000206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00277

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0122

AC:

17739

AN:

1459456

Hom.:

146

Cov.:

AF XY:

0.0118

AC XY:

8565

AN XY:

725792

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00256

Gnomad4 ASJ exome

AF:

0.000231

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00288

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.00818

GnomAD4 genome

AF:

0.00829

AC:

1262

AN:

152212

Hom.:

Cov.:

AF XY:

0.00849

AC XY:

632

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0132

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.00699

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00206

AC:

ESP6500EA

AF:

0.00936

AC:

ExAC

AF:

0.00948

AC:

1146

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.48

N;N

REVEL

Benign

0.055

Sift

Benign

0.28

.;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0010

B;.

Vest4

0.32

MVP

0.22

MPC

1.9

ClinPred

0.021

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over