Genetic Variant NFKBIL1:c.58-141G>C (chr6-31548022-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005007.4(NFKBIL1):c.58-141G>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NFKBIL1
NM_005007.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.769

Publications

42 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:

ATP6V1G2 (HGNC:862): (ATPase H+ transporting V1 subunit G2) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of three V1 domain G subunit proteins. This gene had previous gene symbols of ATP6G and ATP6G2. Alternatively spliced transcript variants encoding different isoforms have been described. Read-through transcription also exists between this gene and the downstream DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
NFKBIL1	NM_005007.4 link	c.58-141G>C	intron_variant	Intron 1 of 3	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2 link	c.58-141G>C	intron_variant	Intron 1 of 3		NP_001138433.1
NFKBIL1	NM_001144962.2 link	c.-12-141G>C	intron_variant	Intron 1 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2 link	c.-12-141G>C	intron_variant	Intron 1 of 3		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9 link	c.58-141G>C		intron_variant	Intron 1 of 3	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

989466

Hom.:

AF XY:

0.00

AC XY:

AN XY:

496038

African (AFR)

AF:

0.00

AC:

AN:

22106

American (AMR)

AF:

0.00

AC:

AN:

23688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18248

East Asian (EAS)

AF:

0.00

AC:

AN:

33808

South Asian (SAS)

AF:

0.00

AC:

AN:

60760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4600

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

742932

Other (OTH)

AF:

0.00

AC:

AN:

44030

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

5305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

(source)

DANN

Benign

0.72

PhyloP100

-0.77

PromoterAI

0.024

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over