Genetic Variant NFKBIB:c.179+80C>G (chr19-38900291-C-G) – 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.179+80C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,409,268 control chromosomes in the GnomAD database, including 102,496 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 0.32 ( 9882 hom., cov: 32)

Exomes 𝑓: 0.38 ( 92614 hom. )

Consequence

NFKBIB
NM_002503.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.448

Publications

18 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:

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=-0.7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIB	NM_002503.5 link	c.179+80C>G		intron_variant	Intron 1 of 5	ENST00000313582.6	NP_002494.2	Q15653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIB	ENST00000313582.6 link	c.179+80C>G		intron_variant	Intron 1 of 5	1	NM_002503.5	ENSP00000312988.5		Q15653-1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49235

AN:

151996

Hom.:

9872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0895

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.453

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.378

AC:

475175

AN:

1257154

Hom.:

92614

AF XY:

0.381

AC XY:

233675

AN XY:

613682

show subpopulations

African (AFR)

AF:

0.0772

AC:

2066

AN:

26748

American (AMR)

AF:

0.534

AC:

10958

AN:

20524

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

7300

AN:

19194

East Asian (EAS)

AF:

0.591

AC:

19460

AN:

32942

South Asian (SAS)

AF:

0.469

AC:

30809

AN:

65622

European-Finnish (FIN)

AF:

0.439

AC:

16012

AN:

36508

Middle Eastern (MID)

AF:

0.365

AC:

1883

AN:

5164

European-Non Finnish (NFE)

AF:

0.367

AC:

366523

AN:

997838

Other (OTH)

AF:

0.383

AC:

20164

AN:

52614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

14571

29141

43712

58282

72853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12112

24224

36336

48448

60560

<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:

0.324

AC:

49249

AN:

152114

Hom.:

9882

Cov.:

AF XY:

0.336

AC XY:

24965

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0892

AC:

3706

AN:

41540

American (AMR)

AF:

0.504

AC:

7694

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1340

AN:

3464

East Asian (EAS)

AF:

0.590

AC:

3043

AN:

5160

South Asian (SAS)

AF:

0.486

AC:

2339

AN:

4812

European-Finnish (FIN)

AF:

0.453

AC:

4796

AN:

10578

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.371

AC:

25217

AN:

67970

Other (OTH)

AF:

0.346

AC:

729

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1539

3078

4617

6156

7695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.334

Hom.:

1337

Bravo

AF:

0.317

Asia WGS

AF:

0.555

AC:

1930

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.7

(source)

DANN

Benign

0.75

PhyloP100

-0.45

PromoterAI

0.041

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over