rs3219183

Positions:

• chr6-31548586-C-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.334+147C>G		intron_variant		ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.334+147C>G		intron_variant			NP_001138433.1
NFKBIL1	NM_001144962.2	c.265+147C>G		intron_variant			NP_001138434.1
NFKBIL1	NM_001144963.2	c.265+147C>G		intron_variant			NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.334+147C>G		intron_variant		1	NM_005007.4	ENSP00000365318	P4

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

Gnomad4 AFR exome AF: 0.0145

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0845

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0657

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.0487

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

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.0955

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0421

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

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: rs3219183; hg19: chr6-31516363;