chr6-31557542-C-G

Variant names:

• chr6-31557542-C-G
• rs2239707
• NM_005007.4:c.335-86C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005007.4(NFKBIL1):​c.335-86C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000106 in 939,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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>G		intron	N/A	NP_004998.3
	NFKBIL1	NM_001144961.2		c.335-86C>G		intron	N/A	NP_001138433.1
	NFKBIL1	NM_001144962.2		c.266-86C>G		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>G		intron	N/A	ENSP00000365318.4
	NFKBIL1	ENST00000376145.8	TSL:1	c.335-86C>G		intron	N/A	ENSP00000365315.4
	NFKBIL1	ENST00000376146.8	TSL:4	c.266-86C>G		intron	N/A	ENSP00000365316.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000106 AC: 1 AN: 939852 Hom.: 0 AF XY: 0.00000214 AC XY: 1 AN XY: 467434

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21732

American (AMR) AF: 0.00 AC: 0 AN: 21704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16074

East Asian (EAS) AF: 0.00 AC: 0 AN: 33266

South Asian (SAS) AF: 0.00 AC: 0 AN: 46296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2872

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 714944

Other (OTH) AF: 0.00 AC: 0 AN: 41188

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74208

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 112459

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.71
PhyloP100		0.12

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;