rs2071592

chr6-31547563-T-Achr6-31547563-T-Cchr6-31547563-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 1.27

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]

ACMG classification

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	UniProt
NFKBIL1	NM_001144962.2	c.-13+590T>A		intron_variant
NFKBIL1	NM_001144963.2	c.-13+590T>A		intron_variant
NFKBIL1	NM_005007.4			upstream_gene_variant		ENST00000376148.9
NFKBIL1	NM_001144961.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376146.8	c.-13+590T>A		intron_variant		4		A1
ATP6V1G2	ENST00000415099.2	c.202+663A>T		intron_variant		5
NFKBIL1	ENST00000376148.9			upstream_gene_variant		1	NM_005007.4	P4
NFKBIL1	ENST00000376145.8			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55736 AN: 151310 Hom.: 10707 Cov.: 29

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

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

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

Submissions by phenotype

Rheumatoid arthritis Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 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

Other links and lift over

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