dbSNP rs3136645: NFKBIB:c.*302T>C (chr19-38908009-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000572515.5(NFKBIB):c.*302T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,132,180 control chromosomes in the GnomAD database, including 22,082 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 0.25 ( 5217 hom., cov: 32)

Exomes 𝑓: 0.18 ( 16865 hom. )

Consequence

NFKBIB
ENST00000572515.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

15 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIB	NM_002503.5 link	c.969+350T>C		intron_variant	Intron 5 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.969+350T>C		intron_variant	Intron 5 of 5	1	NM_002503.5	ENSP00000312988.5		Q15653-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37645

AN:

151832

Hom.:

5210

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.178

AC:

174835

AN:

980228

Hom.:

16865

Cov.:

AF XY:

0.178

AC XY:

81809

AN XY:

460334

show subpopulations

African (AFR)

AF:

0.313

AC:

6543

AN:

20920

American (AMR)

AF:

0.360

AC:

2520

AN:

7008

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

2271

AN:

10128

East Asian (EAS)

AF:

0.481

AC:

6490

AN:

13506

South Asian (SAS)

AF:

0.170

AC:

4963

AN:

29254

European-Finnish (FIN)

AF:

0.228

AC:

1973

AN:

8648

Middle Eastern (MID)

AF:

0.189

AC:

438

AN:

2312

European-Non Finnish (NFE)

AF:

0.167

AC:

142213

AN:

852058

Other (OTH)

AF:

0.204

AC:

7424

AN:

36394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

7927

15855

23782

31710

39637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6392

12784

19176

25568

31960

<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:

0.248

AC:

37676

AN:

151952

Hom.:

5217

Cov.:

AF XY:

0.256

AC XY:

19055

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.301

AC:

12461

AN:

41400

American (AMR)

AF:

0.361

AC:

5519

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.224

AC:

777

AN:

3472

East Asian (EAS)

AF:

0.472

AC:

2436

AN:

5164

South Asian (SAS)

AF:

0.176

AC:

846

AN:

4810

European-Finnish (FIN)

AF:

0.254

AC:

2687

AN:

10578

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12243

AN:

67960

Other (OTH)

AF:

0.237

AC:

496

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1423

2846

4269

5692

7115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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.:

13844

Bravo

AF:

0.262

Asia WGS

AF:

0.323

AC:

1126

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.51

(source)

DANN

Benign

0.44

PhyloP100

-1.1

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