Variant chr6-31558588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005007.4(NFKBIL1):c.1123C>T(p.Arg375Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,403,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3482887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NFKBIL1	NM_005007.4 linkuse as main transcript	c.1123C>T	p.Arg375Cys	missense_variant	4/4	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	4/4		NP_001138433.1
NFKBIL1	NM_001144962.2 linkuse as main transcript	c.1054C>T	p.Arg352Cys	missense_variant	4/4		NP_001138434.1
NFKBIL1	NM_001144963.2 linkuse as main transcript	c.1009C>T	p.Arg337Cys	missense_variant	4/4		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9 linkuse as main transcript	c.1123C>T	p.Arg375Cys	missense_variant	4/4	1	NM_005007.4	ENSP00000365318	P4	Q9UBC1-1
NFKBIL1	ENST00000376145.8 linkuse as main transcript	c.1078C>T	p.Arg360Cys	missense_variant	4/4	1		ENSP00000365315		Q9UBC1-3
NFKBIL1	ENST00000376146.8 linkuse as main transcript	c.1054C>T	p.Arg352Cys	missense_variant	4/4	4		ENSP00000365316	A1	Q9UBC1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1403984

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

692876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1123C>T (p.R375C) alteration is located in exon 4 (coding exon 4) of the NFKBIL1 gene. This alteration results from a C to T substitution at nucleotide position 1123, causing the arginine (R) at amino acid position 375 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

T;.;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.91

D;.;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.029

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.53

MutPred

0.40

.;Loss of MoRF binding (P = 0.0031);.;

MVP

0.24

MPC

1.9

ClinPred

0.99

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over