rs3219184

Positions:

• chr6-31547363-A-G

Variant summary

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

The NM_001144962.2(NFKBIL1):​c.-13+390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 151,712 control chromosomes in the GnomAD database, including 754 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 0.083 (754 hom., cov: 31)
• Consequence: NFKBIL1 NM_001144962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

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=-1.19).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIL1	NM_001144962.2	c.-13+390A>G		intron_variant
NFKBIL1	NM_001144963.2	c.-13+390A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376146.8	c.-13+390A>G		intron_variant		4		A1
ATP6V1G2	ENST00000415099.2	c.202+863T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12540 AN: 151592 Hom.: 753 Cov.: 31

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0895

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0720

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

GnomAD4 genome AF: 0.0828 AC: 12557 AN: 151712 Hom.: 754 Cov.: 31 AF XY: 0.0926 AC XY: 6863 AN XY: 74136

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.0572

Gnomad4 ASJ AF: 0.0895

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.0733

Gnomad4 OTH AF: 0.0722

Alfa AF: 0.0715 Hom.: 109

Bravo AF: 0.0638

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	2.7
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3219184; hg19: chr6-31515140;