rs2071592

Variant names:

• chr6-31547563-T-A
• rs2071592
• NM_001144962.2:c.-13+590T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31547563-T-A
• chr6-31547563-T-C
• chr6-31547563-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 59 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=-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 rank	MANE	Protein	UniProt
NFKBIL1	NM_001144962.2	c.-13+590T>A		intron_variant	Intron 1 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2	c.-13+590T>A		intron_variant	Intron 1 of 3		NP_001138435.1
NFKBIL1	NM_005007.4	c.-132T>A		upstream_gene_variant		ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.-132T>A		upstream_gene_variant			NP_001138433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.-132T>A		upstream_gene_variant		1	NM_005007.4	ENSP00000365318.4

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

African (AFR) AF: 0.489 AC: 4741 AN: 9688

American (AMR) AF: 0.326 AC: 4422 AN: 13560

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3197 AN: 12312

East Asian (EAS) AF: 0.405 AC: 10821 AN: 26714

South Asian (SAS) AF: 0.285 AC: 9866 AN: 34590

European-Finnish (FIN) AF: 0.300 AC: 8641 AN: 28838

Middle Eastern (MID) AF: 0.323 AC: 599 AN: 1852

European-Non Finnish (NFE) AF: 0.321 AC: 82231 AN: 256170

Other (OTH) AF: 0.336 AC: 7885 AN: 23490

GnomAD4 genome AF: 0.368 AC: 55784 AN: 151432 Hom.: 10718 Cov.: 29 AF XY: 0.365 AC XY: 26993 AN XY: 73978

African (AFR) AF: 0.487 AC: 20052 AN: 41174

American (AMR) AF: 0.345 AC: 5242 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2409 AN: 5120

South Asian (SAS) AF: 0.280 AC: 1341 AN: 4790

European-Finnish (FIN) AF: 0.281 AC: 2948 AN: 10480

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21810 AN: 67898

Other (OTH) AF: 0.345 AC: 721 AN: 2092

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

Feb 01, 2003

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.9
DANN	Benign	0.59
PhyloP100		1.3
PromoterAI		0.26	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

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