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GeneBe

6-31557671-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_005007.4(NFKBIL1):c.378C>T(p.Ser126=) 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 (★).

Frequency

Genomes: 𝑓 0.13 ( 1585 hom., cov: 32)
Exomes 𝑓: 0.15 ( 17953 hom. )

Consequence

NFKBIL1
NM_005007.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.723
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-31557671-C-T is Benign according to our data. Variant chr6-31557671-C-T is described in ClinVar as [Benign]. Clinvar id is 3060308.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.723 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
NFKBIL1NM_005007.4 linkuse as main transcriptc.378C>T p.Ser126= synonymous_variant 3/4 ENST00000376148.9
NFKBIL1NM_001144961.2 linkuse as main transcriptc.378C>T p.Ser126= synonymous_variant 3/4
NFKBIL1NM_001144962.2 linkuse as main transcriptc.309C>T p.Ser103= synonymous_variant 3/4
NFKBIL1NM_001144963.2 linkuse as main transcriptc.309C>T p.Ser103= synonymous_variant 3/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NFKBIL1ENST00000376148.9 linkuse as main transcriptc.378C>T p.Ser126= synonymous_variant 3/41 NM_005007.4 P4Q9UBC1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.132
AC:
20002
AN:
151982
Hom.:
1587
Cov.:
32
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
GnomAD3 exomes
AF:
0.163
AC:
38474
AN:
236606
Hom.:
3369
AF XY:
0.169
AC XY:
21639
AN XY:
128228
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 SAS exome
AF:
0.228
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.:
33
AF XY:
0.157
AC XY:
110221
AN XY:
702874
show subpopulations
Gnomad4 AFR exome
AF:
0.0580
Gnomad4 AMR exome
AF:
0.126
Gnomad4 ASJ exome
AF:
0.228
Gnomad4 EAS exome
AF:
0.250
Gnomad4 SAS exome
AF:
0.232
Gnomad4 FIN exome
AF:
0.173
Gnomad4 NFE exome
AF:
0.145
Gnomad4 OTH exome
AF:
0.158
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.132
AC:
20012
AN:
152100
Hom.:
1585
Cov.:
32
AF XY:
0.136
AC XY:
10083
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0630
Gnomad4 AMR
AF:
0.129
Gnomad4 ASJ
AF:
0.223
Gnomad4 EAS
AF:
0.215
Gnomad4 SAS
AF:
0.232
Gnomad4 FIN
AF:
0.180
Gnomad4 NFE
AF:
0.149
Gnomad4 OTH
AF:
0.144
Alfa
AF:
0.156
Hom.:
3655
Bravo
AF:
0.123
Asia WGS
AF:
0.206
AC:
717
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

NFKBIL1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
Dann
Benign
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2230365; hg19: chr6-31525448; COSMIC: COSV65990787; API