Genetic Variant NFKBIB:c.970-94C>T (chr19-38908637-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_002503.5(NFKBIB):c.970-94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,442,270 control chromosomes in the GnomAD database, including 39,023 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 0.19 ( 3109 hom., cov: 30)

Exomes 𝑓: 0.23 ( 35914 hom. )

Consequence

NFKBIB
NM_002503.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.930

Publications

25 publications found

Variant links:

Genes affected

NFKBIB (HGNC:7798): (NFKB inhibitor beta) The protein encoded by this gene belongs to the NF-kappa-B inhibitor family, which inhibit NF-kappa-B by complexing with, and trapping it in the cytoplasm. Phosphorylation of serine residues on these proteins by kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B, which translocates to the nucleus to function as a transcription factor. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jul 2011]

NFKBIB 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=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIB	NM_002503.5 link	c.970-94C>T		intron_variant	Intron 5 of 5	ENST00000313582.6	NP_002494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIB	ENST00000313582.6 link	c.970-94C>T		intron_variant	Intron 5 of 5	1	NM_002503.5	ENSP00000312988.5

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28083

AN:

151390

Hom.:

3110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.192

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.201

GnomAD4 exome

AF:

0.232

AC:

299712

AN:

1290774

Hom.:

35914

Cov.:

AF XY:

0.235

AC XY:

147866

AN XY:

629072

show subpopulations

African (AFR)

AF:

0.0672

AC:

1765

AN:

26270

American (AMR)

AF:

0.210

AC:

4377

AN:

20840

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

4447

AN:

19028

East Asian (EAS)

AF:

0.158

AC:

4998

AN:

31620

South Asian (SAS)

AF:

0.322

AC:

18993

AN:

58946

European-Finnish (FIN)

AF:

0.189

AC:

8873

AN:

46876

Middle Eastern (MID)

AF:

0.238

AC:

848

AN:

3562

European-Non Finnish (NFE)

AF:

0.236

AC:

243343

AN:

1030806

Other (OTH)

AF:

0.228

AC:

12068

AN:

52826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

10784

21568

32351

43135

53919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8750

17500

26250

35000

43750

<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:

0.185

AC:

28084

AN:

151496

Hom.:

3109

Cov.:

AF XY:

0.184

AC XY:

13608

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.0773

AC:

3193

AN:

41300

American (AMR)

AF:

0.216

AC:

3282

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

809

AN:

3470

East Asian (EAS)

AF:

0.158

AC:

812

AN:

5136

South Asian (SAS)

AF:

0.331

AC:

1595

AN:

4812

European-Finnish (FIN)

AF:

0.180

AC:

1872

AN:

10422

Middle Eastern (MID)

AF:

0.179

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.234

AC:

15878

AN:

67854

Other (OTH)

AF:

0.204

AC:

429

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1073

2147

3220

4294

5367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.205

Hom.:

3629

Bravo

AF:

0.180

Asia WGS

AF:

0.275

AC:

954

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

2.5

(source)

DANN

Benign

0.72

PhyloP100

-0.93

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

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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