6-31557577-C-T

Variant summary

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

The NM_005007.4(NFKBIL1):c.335-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,414,106 control chromosomes in the GnomAD database, including 53 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 0.0016 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (48 hom.)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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=-0.67).
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00116 (1467/1261806) while in subpopulation AMR AF= 0.0456 (1218/26726). AF 95% confidence interval is 0.0434. There are 48 homozygotes in gnomad4_exome. There are 640 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFKBIL1	NM_005007.4	c.335-51C>T		intron_variant		ENST00000376148.9
NFKBIL1	NM_001144961.2	c.335-51C>T		intron_variant
NFKBIL1	NM_001144962.2	c.266-51C>T		intron_variant
NFKBIL1	NM_001144963.2	c.266-51C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.335-51C>T		intron_variant		1	NM_005007.4	P4

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152182 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00729 AC: 1180 AN: 161894 Hom.: 41 AF XY: 0.00574 AC XY: 493 AN XY: 85946

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0606

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00435

Gnomad SAS exome AF: 0.000157

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000376

Gnomad OTH exome AF: 0.00280

GnomAD4 exome AF: 0.00116 AC: 1467 AN: 1261806 Hom.: 48 Cov.: 18 AF XY: 0.00104 AC XY: 640 AN XY: 617150

Gnomad4 AFR exome AF: 0.0000710

Gnomad4 AMR exome AF: 0.0456

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00391

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000678

Gnomad4 OTH exome AF: 0.000556

GnomAD4 genome AF: 0.00160 AC: 243 AN: 152300 Hom.: 5 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74476

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00221 Hom.: 7

Bravo AF: 0.00385

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	12
Dann	Benign	0.86

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: rs3219179; hg19: chr6-31525354;