rs3219183

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-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

African (AFR) AF: 0.0145 AC: 218 AN: 15038

American (AMR) AF: 0.0346 AC: 418 AN: 12068

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 1147 AN: 13570

East Asian (EAS) AF: 0.150 AC: 4019 AN: 26844

South Asian (SAS) AF: 0.143 AC: 4773 AN: 33316

European-Finnish (FIN) AF: 0.0657 AC: 1763 AN: 26844

Middle Eastern (MID) AF: 0.0989 AC: 230 AN: 2326

European-Non Finnish (NFE) AF: 0.0367 AC: 19405 AN: 528226

Other (OTH) AF: 0.0487 AC: 1593 AN: 32702

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

African (AFR) AF: 0.0164 AC: 680 AN: 41578

American (AMR) AF: 0.0341 AC: 521 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.0955 AC: 495 AN: 5184

South Asian (SAS) AF: 0.157 AC: 759 AN: 4832

European-Finnish (FIN) AF: 0.0761 AC: 808 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2827 AN: 68024

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

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
PhyloP100		1.1
PromoterAI		0.0049	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3219183; hg19: chr6-31516363;