6-31547563-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001144962.2(NFKBIL1):​c.-13+590T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 558,646 control chromosomes in the GnomAD database, including 33,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.37 ( 10718 hom., cov: 29)
Exomes 𝑓: 0.33 ( 22467 hom. )

Consequence

NFKBIL1
NM_001144962.2 intron

Scores

2

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.27
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.01).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NFKBIL1NM_001144962.2 linkuse as main transcriptc.-13+590T>A intron_variant NP_001138434.1
NFKBIL1NM_001144963.2 linkuse as main transcriptc.-13+590T>A intron_variant NP_001138435.1
NFKBIL1NM_005007.4 linkuse as main transcript upstream_gene_variant ENST00000376148.9 NP_004998.3
NFKBIL1NM_001144961.2 linkuse as main transcript upstream_gene_variant NP_001138433.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NFKBIL1ENST00000376146.8 linkuse as main transcriptc.-13+590T>A intron_variant 4 ENSP00000365316 A1Q9UBC1-2
ATP6V1G2ENST00000415099.2 linkuse as main transcriptc.202+663A>T intron_variant 5 ENSP00000390148
NFKBIL1ENST00000376148.9 linkuse as main transcript upstream_gene_variant 1 NM_005007.4 ENSP00000365318 P4Q9UBC1-1
NFKBIL1ENST00000376145.8 linkuse as main transcript upstream_gene_variant 1 ENSP00000365315 Q9UBC1-3

Frequencies

GnomAD3 genomes
AF:
0.368
AC:
55736
AN:
151310
Hom.:
10707
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.487
Gnomad AMI
AF:
0.333
Gnomad AMR
AF:
0.344
Gnomad ASJ
AF:
0.249
Gnomad EAS
AF:
0.470
Gnomad SAS
AF:
0.279
Gnomad FIN
AF:
0.281
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.321
Gnomad OTH
AF:
0.346
GnomAD4 exome
AF:
0.325
AC:
132403
AN:
407214
Hom.:
22467
Cov.:
5
AF XY:
0.322
AC XY:
69261
AN XY:
214892
show subpopulations
Gnomad4 AFR exome
AF:
0.489
Gnomad4 AMR exome
AF:
0.326
Gnomad4 ASJ exome
AF:
0.260
Gnomad4 EAS exome
AF:
0.405
Gnomad4 SAS exome
AF:
0.285
Gnomad4 FIN exome
AF:
0.300
Gnomad4 NFE exome
AF:
0.321
Gnomad4 OTH exome
AF:
0.336
GnomAD4 genome
AF:
0.368
AC:
55784
AN:
151432
Hom.:
10718
Cov.:
29
AF XY:
0.365
AC XY:
26993
AN XY:
73978
show subpopulations
Gnomad4 AFR
AF:
0.487
Gnomad4 AMR
AF:
0.345
Gnomad4 ASJ
AF:
0.249
Gnomad4 EAS
AF:
0.471
Gnomad4 SAS
AF:
0.280
Gnomad4 FIN
AF:
0.281
Gnomad4 NFE
AF:
0.321
Gnomad4 OTH
AF:
0.345
Alfa
AF:
0.332
Hom.:
4852
Bravo
AF:
0.379
Asia WGS
AF:
0.307
AC:
1069
AN:
3478

ClinVar

Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Rheumatoid arthritis Other:1
risk factor, no assertion criteria providedliterature onlyOMIMFeb 01, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
7.9
DANN
Benign
0.59

Splicing

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: rs2071592; hg19: chr6-31515340; COSMIC: COSV58215444; API