rs3219184

Variant names:

• chr6-31547363-A-G
• rs3219184
• NM_001144962.2:c.-13+390A>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+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
• Publications: 7 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=-1.19).
• 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 rank	MANE	Protein	UniProt
NFKBIL1	NM_001144962.2	c.-13+390A>G		intron_variant	Intron 1 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2	c.-13+390A>G		intron_variant	Intron 1 of 3		NP_001138435.1
NFKBIL1	NM_005007.4	c.-332A>G		upstream_gene_variant		ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.-332A>G		upstream_gene_variant			NP_001138433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376146.8	c.-13+390A>G		intron_variant	Intron 1 of 3	4		ENSP00000365316.4
ATP6V1G2	ENST00000415099.2	c.202+863T>C		intron_variant	Intron 1 of 2	5		ENSP00000390148.2
NFKBIL1	ENST00000376148.9	c.-332A>G		upstream_gene_variant		1	NM_005007.4	ENSP00000365318.4
NFKBIL1	ENST00000376145.8	c.-332A>G		upstream_gene_variant		1		ENSP00000365315.4

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

African (AFR) AF: 0.0539 AC: 2231 AN: 41368

American (AMR) AF: 0.0572 AC: 871 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0895 AC: 310 AN: 3464

East Asian (EAS) AF: 0.104 AC: 535 AN: 5146

South Asian (SAS) AF: 0.170 AC: 813 AN: 4788

European-Finnish (FIN) AF: 0.241 AC: 2531 AN: 10504

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0733 AC: 4976 AN: 67910

Other (OTH) AF: 0.0722 AC: 152 AN: 2104

Alfa AF: 0.0693 Hom.: 227

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
PhyloP100		-0.82
PromoterAI		0.084	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: rs3219184; hg19: chr6-31515140;