rs3093949

Variant names:

• chr6-31557407-C-T
• rs3093949
• NM_005007.4:c.335-221C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005007.4(NFKBIL1):​c.335-221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,980 control chromosomes in the GnomAD database, including 10,732 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 0.37 (10732 hom., cov: 32)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.335-221C>T		intron_variant	Intron 2 of 3	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.335-221C>T		intron_variant	Intron 2 of 3		NP_001138433.1
NFKBIL1	NM_001144962.2	c.266-221C>T		intron_variant	Intron 2 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2	c.266-221C>T		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.335-221C>T		intron_variant	Intron 2 of 3	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56308 AN: 151860 Hom.: 10727 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.371 AC: 56347 AN: 151980 Hom.: 10732 Cov.: 32 AF XY: 0.367 AC XY: 27269 AN XY: 74314

African (AFR) AF: 0.464 AC: 19205 AN: 41420

American (AMR) AF: 0.338 AC: 5171 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2431 AN: 5164

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4822

European-Finnish (FIN) AF: 0.302 AC: 3194 AN: 10566

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22979 AN: 67944

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.353 Hom.: 3830

Bravo AF: 0.377

Asia WGS AF: 0.328 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.89
PhyloP100		-0.29
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: rs3093949; hg19: chr6-31525184;