Genetic Variant NM_005007.4:c.578A>C (chr6-31558043-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005007.4(NFKBIL1):c.578A>C(p.Gln193Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NFKBIL1
NM_005007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.791

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.085264206).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005007.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFKBIL1	NM_005007.4	MANE Select	c.578A>C	p.Gln193Pro	missense	Exon 4 of 4	NP_004998.3
NFKBIL1	NM_001144961.2		c.533A>C	p.Gln178Pro	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
NFKBIL1	NM_001144962.2		c.509A>C	p.Gln170Pro	missense	Exon 4 of 4	NP_001138434.1	Q5STV6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.578A>C	p.Gln193Pro	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
NFKBIL1	ENST00000376145.8	TSL:1	c.533A>C	p.Gln178Pro	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
NFKBIL1	ENST00000376146.8	TSL:4	c.509A>C	p.Gln170Pro	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1253004

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

621204

African (AFR)

AF:

0.00

AC:

AN:

27420

American (AMR)

AF:

0.00

AC:

AN:

38428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18806

East Asian (EAS)

AF:

0.00

AC:

AN:

22044

South Asian (SAS)

AF:

0.00

AC:

AN:

83486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4576

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

976388

Other (OTH)

AF:

0.00

AC:

AN:

46906

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.67

M_CAP

Benign

0.0049

MetaRNN

Benign

0.085

MetaSVM

Benign

-1.0

PhyloP100

0.79

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.22

REVEL

Benign

0.038

Sift

Benign

0.38

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.16

MutPred

0.36

Gain of helix (P = 0.0034)

MVP

0.22

MPC

0.75

ClinPred

0.056

GERP RS

0.36

gMVP

0.24

Mutation Taster

=72/28

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over