rs2071591

Positions:

• chr6-31548022-G-A
• chr6-31548022-G-C

Variant summary

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

The NM_005007.4(NFKBIL1):​c.58-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,139,426 control chromosomes in the GnomAD database, including 73,423 homozygotes. 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: 𝑓 0.38 (11676 hom., cov: 31)
  • Exomes 𝑓: 0.35 (61747 hom.)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.58-141G>A		intron_variant		ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.58-141G>A		intron_variant			NP_001138433.1
NFKBIL1	NM_001144962.2	c.-12-141G>A		intron_variant			NP_001138434.1
NFKBIL1	NM_001144963.2	c.-12-141G>A		intron_variant			NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.58-141G>A		intron_variant		1	NM_005007.4	ENSP00000365318	P4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58360 AN: 151800 Hom.: 11666 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.348 AC: 343217 AN: 987508 Hom.: 61747 AF XY: 0.345 AC XY: 170623 AN XY: 495040

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.384 AC: 58406 AN: 151918 Hom.: 11676 Cov.: 31 AF XY: 0.381 AC XY: 28279 AN XY: 74240

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.353

Alfa AF: 0.349 Hom.: 4764

Bravo AF: 0.392

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs2071591; hg19: chr6-31515799; COSMIC: COSV58214743; COSMIC: COSV58214743;