rs3219183

Variant names:

• chr6-31548586-C-G
• rs3219183
• NM_005007.4:c.334+147C>G

Variant summary

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

The NM_005007.4(NFKBIL1):​c.334+147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 843,256 control chromosomes in the GnomAD database, including 1,576 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 0.043 (248 hom., cov: 32)
  • Exomes 𝑓: 0.049 (1328 hom.)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.334+147C>G		intron_variant	Intron 2 of 3	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.334+147C>G		intron_variant	Intron 2 of 3		NP_001138433.1
NFKBIL1	NM_001144962.2	c.265+147C>G		intron_variant	Intron 2 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2	c.265+147C>G		intron_variant	Intron 2 of 3		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.334+147C>G		intron_variant	Intron 2 of 3	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6503 AN: 152204 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0341

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0957

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0486 AC: 33566 AN: 690934 Hom.: 1328 AF XY: 0.0516 AC XY: 17665 AN XY: 342340

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0657

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.0487

GnomAD4 genome AF: 0.0428 AC: 6513 AN: 152322 Hom.: 248 Cov.: 32 AF XY: 0.0474 AC XY: 3529 AN XY: 74490

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0414 Hom.: 32

Bravo AF: 0.0348

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.9
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3219183; hg19: chr6-31516363;