6-31557577-C-T

Variant names:

• chr6-31557577-C-T
• rs3219179
• NM_005007.4:c.335-51C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.67).
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 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 GnomAdExome4. There are 640 alleles in the male GnomAdExome4 subpopulation. Median coverage is 18. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	NM_005007.4	MANE Select	c.335-51C>T		intron	N/A	NP_004998.3
	NFKBIL1	NM_001144961.2		c.335-51C>T		intron	N/A	NP_001138433.1
	NFKBIL1	NM_001144962.2		c.266-51C>T		intron	N/A	NP_001138434.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.335-51C>T		intron	N/A	ENSP00000365318.4
	NFKBIL1	ENST00000376145.8	TSL:1	c.335-51C>T		intron	N/A	ENSP00000365315.4
	NFKBIL1	ENST00000376146.8	TSL:4	c.266-51C>T		intron	N/A	ENSP00000365316.4

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

GnomAD2 exomes AF: 0.00729 AC: 1180 AN: 161894 AF XY: 0.00574

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 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

African (AFR) AF: 0.0000710 AC: 2 AN: 28158

American (AMR) AF: 0.0456 AC: 1218 AN: 26726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18788

East Asian (EAS) AF: 0.00391 AC: 142 AN: 36342

South Asian (SAS) AF: 0.000152 AC: 9 AN: 59202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3488

European-Non Finnish (NFE) AF: 0.0000678 AC: 67 AN: 988908

Other (OTH) AF: 0.000556 AC: 29 AN: 52188

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

African (AFR) AF: 0.0000962 AC: 4 AN: 41562

American (AMR) AF: 0.0140 AC: 214 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00306 Hom.: 13

Bravo AF: 0.00385

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.86
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: rs3219179; hg19: chr6-31525354;