rs2071591

Variant names:

• chr6-31548022-G-A
• rs2071591
• NM_005007.4:c.58-141G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.58-141G>A		intron_variant	Intron 1 of 3	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.58-141G>A		intron_variant	Intron 1 of 3		NP_001138433.1
NFKBIL1	NM_001144962.2	c.-12-141G>A		intron_variant	Intron 1 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2	c.-12-141G>A		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	c.58-141G>A		intron_variant	Intron 1 of 3	1	NM_005007.4	ENSP00000365318.4

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

African (AFR) AF: 0.504 AC: 11130 AN: 22070

American (AMR) AF: 0.329 AC: 7795 AN: 23664

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 4735 AN: 18228

East Asian (EAS) AF: 0.425 AC: 14356 AN: 33784

South Asian (SAS) AF: 0.286 AC: 17391 AN: 60704

European-Finnish (FIN) AF: 0.325 AC: 12747 AN: 39262

Middle Eastern (MID) AF: 0.372 AC: 1708 AN: 4594

European-Non Finnish (NFE) AF: 0.348 AC: 257973 AN: 741232

Other (OTH) AF: 0.350 AC: 15382 AN: 43970

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

African (AFR) AF: 0.502 AC: 20795 AN: 41432

American (AMR) AF: 0.347 AC: 5291 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3466

East Asian (EAS) AF: 0.474 AC: 2448 AN: 5168

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4814

European-Finnish (FIN) AF: 0.315 AC: 3317 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23158 AN: 67948

Other (OTH) AF: 0.353 AC: 744 AN: 2108

Alfa AF: 0.350 Hom.: 5305

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
PhyloP100		-0.77
PromoterAI		-0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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