dbSNP rs2230365: NFKBIL1:p.Ser126Ser (chr6-31557671-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_005007.4(NFKBIL1):c.378C>T(p.Ser126Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,575,870 control chromosomes in the GnomAD database, including 19,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1585 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17953 hom. )

Consequence

NFKBIL1
NM_005007.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.723

Publications

72 publications found

Variant links:

Genes affected

NFKBIL1 (HGNC:7800): (NFKB inhibitor like 1) This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

NFKBIL1 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=-0.44).

BP6

Variant 6-31557671-C-T is Benign according to our data. Variant chr6-31557671-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060308.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.723 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
NFKBIL1	NM_005007.4 link	c.378C>T	p.Ser126Ser	synonymous_variant	Exon 3 of 4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2 link	c.378C>T	p.Ser126Ser	synonymous_variant	Exon 3 of 4		NP_001138433.1
NFKBIL1	NM_001144962.2 link	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 4		NP_001138434.1
NFKBIL1	NM_001144963.2 link	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9 link	c.378C>T	p.Ser126Ser	synonymous_variant	Exon 3 of 4	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20002

AN:

151982

Hom.:

1587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.144

GnomAD2 exomes

AF:

0.163

AC:

38474

AN:

236606

AF XY:

0.169

show subpopulations

Gnomad AFR exome

AF:

0.0574

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.154

AC:

218556

AN:

1423770

Hom.:

17953

Cov.:

AF XY:

0.157

AC XY:

110221

AN XY:

702874

show subpopulations

African (AFR)

AF:

0.0580

AC:

1887

AN:

32526

American (AMR)

AF:

0.126

AC:

5230

AN:

41362

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

5672

AN:

24866

East Asian (EAS)

AF:

0.250

AC:

9636

AN:

38548

South Asian (SAS)

AF:

0.232

AC:

18983

AN:

81744

European-Finnish (FIN)

AF:

0.173

AC:

9161

AN:

52810

Middle Eastern (MID)

AF:

0.207

AC:

1157

AN:

5582

European-Non Finnish (NFE)

AF:

0.145

AC:

157569

AN:

1087688

Other (OTH)

AF:

0.158

AC:

9261

AN:

58644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

9313

18627

27940

37254

46567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5778

11556

17334

23112

28890

<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:

0.132

AC:

20012

AN:

152100

Hom.:

1585

Cov.:

AF XY:

0.136

AC XY:

10083

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0630

AC:

2616

AN:

41514

American (AMR)

AF:

0.129

AC:

1970

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

772

AN:

3468

East Asian (EAS)

AF:

0.215

AC:

1114

AN:

5170

South Asian (SAS)

AF:

0.232

AC:

1115

AN:

4812

European-Finnish (FIN)

AF:

0.180

AC:

1898

AN:

10568

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10133

AN:

67972

Other (OTH)

AF:

0.144

AC:

303

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

877

1755

2632

3510

4387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.150

Hom.:

7241

Bravo

AF:

0.123

Asia WGS

AF:

0.206

AC:

717

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NFKBIL1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.7

(source)

DANN

Benign

0.68

PhyloP100

-0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over