chr6-31558279-C-G

Variant names:

• chr6-31558279-C-G
• rs200733771
• NM_005007.4:c.814C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_005007.4(NFKBIL1):​c.814C>G​(p.Arg272Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,586,526 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (5 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0210
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002812922).
• BP6: Variant 6-31558279-C-G is Benign according to our data. Variant chr6-31558279-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3058781.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 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.814C>G	p.Arg272Gly	missense	Exon 4 of 4	NP_004998.3
	NFKBIL1	NM_001144961.2		c.769C>G	p.Arg257Gly	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
	NFKBIL1	NM_001144962.2		c.745C>G	p.Arg249Gly	missense	Exon 4 of 4	NP_001138434.1	Q5STV6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	ENST00000376148.9	TSL:1 MANE Select	c.814C>G	p.Arg272Gly	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
	NFKBIL1	ENST00000376145.8	TSL:1	c.769C>G	p.Arg257Gly	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
	NFKBIL1	ENST00000376146.8	TSL:4	c.745C>G	p.Arg249Gly	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152122 Hom.: 0 Cov.: 31

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: 0.00498

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000989 AC: 201 AN: 203138 AF XY: 0.00141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000567

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000427 AC: 613 AN: 1434286 Hom.: 5 Cov.: 35 AF XY: 0.000636 AC XY: 452 AN XY: 710598

African (AFR) AF: 0.0000304 AC: 1 AN: 32914

American (AMR) AF: 0.00 AC: 0 AN: 40016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 38968

South Asian (SAS) AF: 0.00675 AC: 562 AN: 83268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50612

Middle Eastern (MID) AF: 0.000352 AC: 2 AN: 5684

European-Non Finnish (NFE) AF: 0.0000300 AC: 33 AN: 1098448

Other (OTH) AF: 0.000253 AC: 15 AN: 59234

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152240 Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4818

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: 0.000103 AC: 7 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000157 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.000942 AC: 110

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NFKBIL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.4
DANN	Benign	0.92
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.021
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.017
Sift	Benign	0.16	T
Sift4G	Benign	0.34	T
Polyphen		0.011	B
Vest4		0.051
MVP		0.093
MPC		0.78
ClinPred		0.0091	T
GERP RS		2.8
gMVP		0.40
Mutation Taster		=99/1	polymorphism

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: rs200733771; hg19: chr6-31526056;