NM_001144962.2:c.-13+590T>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144962.2(NFKBIL1):​c.-13+590T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000245 in 407,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: NFKBIL1 NM_001144962.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144962.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	NM_001144962.2		c.-13+590T>G		intron	N/A	NP_001138434.1
	NFKBIL1	NM_001144963.2		c.-13+590T>G		intron	N/A	NP_001138435.1
	NFKBIL1	NM_005007.4	MANE Select	c.-132T>G		upstream_gene	N/A	NP_004998.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	ENST00000376146.8	TSL:4	c.-13+590T>G		intron	N/A	ENSP00000365316.4
	ATP6V1G2	ENST00000415099.2	TSL:5	c.202+663A>C		intron	N/A	ENSP00000390148.2
	NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.-132T>G		upstream_gene	N/A	ENSP00000365318.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000245 AC: 1 AN: 407800 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 215200

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9704

American (AMR) AF: 0.00 AC: 0 AN: 13586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12320

East Asian (EAS) AF: 0.00 AC: 0 AN: 26734

South Asian (SAS) AF: 0.00 AC: 0 AN: 34660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1852

European-Non Finnish (NFE) AF: 0.00000390 AC: 1 AN: 256554

Other (OTH) AF: 0.00 AC: 0 AN: 23528

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.0
DANN	Benign	0.47
PhyloP100		1.3
PromoterAI		0.31	Neutral

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;