6-31557542-C-T

Variant names:

• chr6-31557542-C-T
• rs2239707
• NM_005007.4:c.335-86C>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.335-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 1,089,910 control chromosomes in the GnomAD database, including 269,884 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 0.74 (42735 hom., cov: 32)
  • Exomes 𝑓: 0.69 (227149 hom.)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 37 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005007.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	NM_005007.4	MANE Select	c.335-86C>T		intron	N/A	NP_004998.3
	NFKBIL1	NM_001144961.2		c.335-86C>T		intron	N/A	NP_001138433.1
	NFKBIL1	NM_001144962.2		c.266-86C>T		intron	N/A	NP_001138434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.335-86C>T		intron	N/A	ENSP00000365318.4
	NFKBIL1	ENST00000376145.8	TSL:1	c.335-86C>T		intron	N/A	ENSP00000365315.4
	NFKBIL1	ENST00000376146.8	TSL:4	c.266-86C>T		intron	N/A	ENSP00000365316.4

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112987 AN: 151942 Hom.: 42686 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.760

GnomAD4 exome AF: 0.694 AC: 651010 AN: 937850 Hom.: 227149 AF XY: 0.694 AC XY: 323919 AN XY: 466502

African (AFR) AF: 0.881 AC: 19132 AN: 21710

American (AMR) AF: 0.767 AC: 16599 AN: 21654

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 12318 AN: 16048

East Asian (EAS) AF: 0.659 AC: 21918 AN: 33246

South Asian (SAS) AF: 0.712 AC: 32895 AN: 46218

European-Finnish (FIN) AF: 0.634 AC: 26434 AN: 41722

Middle Eastern (MID) AF: 0.759 AC: 2173 AN: 2862

European-Non Finnish (NFE) AF: 0.688 AC: 490581 AN: 713254

Other (OTH) AF: 0.704 AC: 28960 AN: 41136

GnomAD4 genome AF: 0.744 AC: 113101 AN: 152060 Hom.: 42735 Cov.: 32 AF XY: 0.742 AC XY: 55110 AN XY: 74292

African (AFR) AF: 0.869 AC: 36070 AN: 41522

American (AMR) AF: 0.769 AC: 11773 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2648 AN: 3470

East Asian (EAS) AF: 0.711 AC: 3673 AN: 5164

South Asian (SAS) AF: 0.700 AC: 3379 AN: 4824

European-Finnish (FIN) AF: 0.631 AC: 6647 AN: 10534

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.682 AC: 46314 AN: 67936

Other (OTH) AF: 0.761 AC: 1602 AN: 2104

Alfa AF: 0.710 Hom.: 112459

Bravo AF: 0.761

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.80
PhyloP100		0.12
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: rs2239707; hg19: chr6-31525319;