rs2523500

Positions:

• chr6-31550577-G-A

Variant summary

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

The NM_005007.4(NFKBIL1):​c.334+2138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,990 control chromosomes in the GnomAD database, including 36,035 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 0.69 (36035 hom., cov: 31)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIL1	NM_005007.4	c.334+2138G>A		intron_variant		ENST00000376148.9
NFKBIL1	NM_001144961.2	c.334+2138G>A		intron_variant
NFKBIL1	NM_001144962.2	c.265+2138G>A		intron_variant
NFKBIL1	NM_001144963.2	c.265+2138G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.334+2138G>A		intron_variant		1	NM_005007.4	P4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104189 AN: 151872 Hom.: 35993 Cov.: 31

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.686 AC: 104287 AN: 151990 Hom.: 36035 Cov.: 31 AF XY: 0.691 AC XY: 51360 AN XY: 74276

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.735

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.684

Alfa AF: 0.645 Hom.: 30464

Bravo AF: 0.676

Asia WGS AF: 0.723 AC: 2516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.72

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: rs2523500; hg19: chr6-31518354;