chr6-31558085-G-A

Variant names:

• chr6-31558085-G-A
• rs766761473
• NM_005007.4:c.620G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005007.4(NFKBIL1):​c.620G>A​(p.Arg207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000555 in 1,477,646 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000059 (0 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.976
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03242472).

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.620G>A	p.Arg207Gln	missense	Exon 4 of 4	NP_004998.3
	NFKBIL1	NM_001144961.2		c.575G>A	p.Arg192Gln	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
	NFKBIL1	NM_001144962.2		c.551G>A	p.Arg184Gln	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.620G>A	p.Arg207Gln	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
	NFKBIL1	ENST00000376145.8	TSL:1	c.575G>A	p.Arg192Gln	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
	NFKBIL1	ENST00000376146.8	TSL:4	c.551G>A	p.Arg184Gln	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 146976 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000675

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000220

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000903 AC: 22 AN: 243712 AF XY: 0.0000901

Gnomad AFR exome AF: 0.0000670

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.000202

Gnomad EAS exome AF: 0.000712

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000276

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000594 AC: 79 AN: 1330670 Hom.: 0 Cov.: 53 AF XY: 0.0000576 AC XY: 38 AN XY: 660260

African (AFR) AF: 0.0000677 AC: 2 AN: 29562

American (AMR) AF: 0.0000985 AC: 4 AN: 40602

Ashkenazi Jewish (ASJ) AF: 0.000140 AC: 3 AN: 21362

East Asian (EAS) AF: 0.000436 AC: 13 AN: 29794

South Asian (SAS) AF: 0.0000353 AC: 3 AN: 84980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39478

Middle Eastern (MID) AF: 0.000204 AC: 1 AN: 4904

European-Non Finnish (NFE) AF: 0.0000447 AC: 46 AN: 1028392

Other (OTH) AF: 0.000136 AC: 7 AN: 51596

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 146976 Hom.: 0 Cov.: 31 AF XY: 0.0000279 AC XY: 2 AN XY: 71614

African (AFR) AF: 0.00 AC: 0 AN: 40494

American (AMR) AF: 0.0000675 AC: 1 AN: 14810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.000220 AC: 1 AN: 4540

South Asian (SAS) AF: 0.00 AC: 0 AN: 4232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66592

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.0000672 Hom.: 0

ExAC AF: 0.0000840 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.98
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.034
Sift	Benign	0.42	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.28		Loss of loop (P = 9e-04)
MVP		0.24
MPC		0.71
ClinPred		0.036	T
GERP RS		0.33
gMVP		0.31
Mutation Taster		=97/3	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: rs766761473; hg19: chr6-31525862; COSMIC: COSV65990305; COSMIC: COSV65990305;