rs3219185

Positions:

• chr6-31547301-C-G
• chr6-31547301-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001144962.2(NFKBIL1):​c.-13+328C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 151,650 control chromosomes in the GnomAD database, including 14 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 0.0092 (14 hom., cov: 31)
• Consequence: NFKBIL1 NM_001144962.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-1.16).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0092 (1395/151650) while in subpopulation AFR AF= 0.0263 (1088/41326). AF 95% confidence interval is 0.025. There are 14 homozygotes in gnomad4. There are 687 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFKBIL1	NM_001144962.2	c.-13+328C>G		intron_variant			NP_001138434.1
NFKBIL1	NM_001144963.2	c.-13+328C>G		intron_variant			NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376146.8	c.-13+328C>G		intron_variant		4		ENSP00000365316.4
ATP6V1G2	ENST00000415099.2	c.202+925G>C		intron_variant		5		ENSP00000390148.2

Frequencies

GnomAD3 genomes AF: 0.00919 AC: 1392 AN: 151536 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0130

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.00920 AC: 1395 AN: 151650 Hom.: 14 Cov.: 31 AF XY: 0.00927 AC XY: 687 AN XY: 74092

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.0000949

Gnomad4 NFE AF: 0.000574

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00111 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.0110 AC: 38 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	3.1
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3219185; hg19: chr6-31515078;