Genetic Variant NFKBIL1:c.335-51C>T (chr6-31557577-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005007.4(NFKBIL1):c.335-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,414,106 control chromosomes in the GnomAD database, including 53 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 0.0016 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 48 hom. )

Consequence

NFKBIL1
NM_005007.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295

Publications

1 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:

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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=-0.67).

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00116 (1467/1261806) while in subpopulation AMR AF = 0.0456 (1218/26726). AF 95% confidence interval is 0.0434. There are 48 homozygotes in GnomAdExome4. There are 640 alleles in the male GnomAdExome4 subpopulation. Median coverage is 18. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4 link	c.335-51C>T	intron_variant	Intron 2 of 3	ENST00000376148.9	NP_004998.3	Q9UBC1-1A8K778
NFKBIL1	NM_001144961.2 link	c.335-51C>T	intron_variant	Intron 2 of 3		NP_001138433.1	Q9UBC1-3A0A0A0MRT5A8K778
NFKBIL1	NM_001144962.2 link	c.266-51C>T	intron_variant	Intron 2 of 3		NP_001138434.1	Q9UBC1-2Q5STV6
NFKBIL1	NM_001144963.2 link	c.266-51C>T	intron_variant	Intron 2 of 3		NP_001138435.1	Q9UBC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9 link	c.335-51C>T		intron_variant	Intron 2 of 3	1	NM_005007.4	ENSP00000365318.4		Q9UBC1-1

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00729

AC:

1180

AN:

161894

AF XY:

0.00574

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0606

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000376

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00116

AC:

1467

AN:

1261806

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

640

AN XY:

617150

show subpopulations

African (AFR)

AF:

0.0000710

AC:

AN:

28158

American (AMR)

AF:

0.0456

AC:

1218

AN:

26726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18788

East Asian (EAS)

AF:

0.00391

AC:

142

AN:

36342

South Asian (SAS)

AF:

0.000152

AC:

AN:

59202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3488

European-Non Finnish (NFE)

AF:

0.0000678

AC:

AN:

988908

Other (OTH)

AF:

0.000556

AC:

AN:

52188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

134

201

268

335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00160

AC:

243

AN:

152300

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

123

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41562

American (AMR)

AF:

0.0140

AC:

214

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00328

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00306

Hom.:

Bravo

AF:

0.00385

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.29

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