rs3219186

Positions:

• chr6-31547195-CT-C
• chr6-31547195-CT-CTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001144962.2(NFKBIL1):​c.-13+231delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57961 hom., cov: 0)
• Consequence: NFKBIL1 NM_001144962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIL1	NM_001144962.2	c.-13+231delT		intron_variant			NP_001138434.1
NFKBIL1	NM_001144963.2	c.-13+231delT		intron_variant			NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376146.8	c.-13+223delT		intron_variant		4		ENSP00000365316.4
ATP6V1G2	ENST00000415099.2	c.203-987delA		intron_variant		5		ENSP00000390148.2

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132094 AN: 151094 Hom.: 57900 Cov.: 0

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.938

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.904

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.874 AC: 132212 AN: 151208 Hom.: 57961 Cov.: 0 AF XY: 0.878 AC XY: 64856 AN XY: 73874

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.967

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.939

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.905

Alfa AF: 0.784 Hom.: 2202

Bravo AF: 0.880

Asia WGS AF: 0.865 AC: 3011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3219186; hg19: chr6-31514972;