rs2239708

Positions:

• chr6-31547986-A-T

Variant summary

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

The NM_005007.4(NFKBIL1):​c.58-177A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 152,056 control chromosomes in the GnomAD database, including 253 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 (253 hom., cov: 31)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIL1	NM_005007.4	c.58-177A>T		intron_variant		ENST00000376148.9
NFKBIL1	NM_001144961.2	c.58-177A>T		intron_variant
NFKBIL1	NM_001144962.2	c.-12-177A>T		intron_variant
NFKBIL1	NM_001144963.2	c.-12-177A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.58-177A>T		intron_variant		1	NM_005007.4	P4

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6545 AN: 151938 Hom.: 253 Cov.: 31

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0953

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0417

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

GnomAD4 genome AF: 0.0431 AC: 6556 AN: 152056 Hom.: 253 Cov.: 31 AF XY: 0.0478 AC XY: 3556 AN XY: 74334

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0765

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0412 Hom.: 28

Bravo AF: 0.0353

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.017
DANN	Benign	0.20

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: rs2239708; hg19: chr6-31515763;