rs3130062

Variant names:

• chr6-31558135-C-T
• rs3130062
• NM_005007.4:c.670C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31558135-C-T
• chr6-31558135-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005007.4(NFKBIL1):​c.670C>T​(p.Arg224Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 1,611,914 control chromosomes in the GnomAD database, including 702,866 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.95 (69357 hom., cov: 31)
  • Exomes 𝑓: 0.93 (633509 hom.)
• Consequence: NFKBIL1 NM_005007.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.01
• Publications: 53 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.35233E-7).
• BP6: Variant 6-31558135-C-T is Benign according to our data. Variant chr6-31558135-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060091.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIL1	NM_005007.4	MANE Select	c.670C>T	p.Arg224Cys	missense	Exon 4 of 4	NP_004998.3
	NFKBIL1	NM_001144961.2		c.625C>T	p.Arg209Cys	missense	Exon 4 of 4	NP_001138433.1	A0A0A0MRT5
	NFKBIL1	NM_001144962.2		c.601C>T	p.Arg201Cys	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.670C>T	p.Arg224Cys	missense	Exon 4 of 4	ENSP00000365318.4	Q9UBC1-1
	NFKBIL1	ENST00000376145.8	TSL:1	c.625C>T	p.Arg209Cys	missense	Exon 4 of 4	ENSP00000365315.4	A0A0A0MRT5
	NFKBIL1	ENST00000376146.8	TSL:4	c.601C>T	p.Arg201Cys	missense	Exon 4 of 4	ENSP00000365316.4	Q5STV6

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145111 AN: 152130 Hom.: 69294 Cov.: 31

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.922

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.971

GnomAD2 exomes AF: 0.955 AC: 231948 AN: 242782 AF XY: 0.956

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.993

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.917

Gnomad NFE exome AF: 0.929

Gnomad OTH exome AF: 0.953

GnomAD4 exome AF: 0.931 AC: 1359001 AN: 1459666 Hom.: 633509 Cov.: 76 AF XY: 0.934 AC XY: 677948 AN XY: 726054

African (AFR) AF: 0.988 AC: 33046 AN: 33456

American (AMR) AF: 0.976 AC: 43580 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 25913 AN: 26108

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39696

South Asian (SAS) AF: 0.999 AC: 85984 AN: 86052

European-Finnish (FIN) AF: 0.919 AC: 48011 AN: 52246

Middle Eastern (MID) AF: 0.999 AC: 5539 AN: 5546

European-Non Finnish (NFE) AF: 0.918 AC: 1020388 AN: 1111610

Other (OTH) AF: 0.942 AC: 56846 AN: 60320

GnomAD4 genome AF: 0.954 AC: 145233 AN: 152248 Hom.: 69357 Cov.: 31 AF XY: 0.955 AC XY: 71064 AN XY: 74426

African (AFR) AF: 0.986 AC: 40980 AN: 41560

American (AMR) AF: 0.967 AC: 14796 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3444 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5157 AN: 5158

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4830

European-Finnish (FIN) AF: 0.922 AC: 9774 AN: 10606

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63025 AN: 68004

Other (OTH) AF: 0.972 AC: 2050 AN: 2110

Alfa AF: 0.938 Hom.: 244709

Bravo AF: 0.959

TwinsUK AF: 0.918 AC: 3404

ALSPAC AF: 0.917 AC: 3534

ESP6500AA AF: 0.983 AC: 2966

ESP6500EA AF: 0.929 AC: 5035

ExAC AF: 0.955 AC: 112326

Asia WGS AF: 0.996 AC: 3465 AN: 3478

EpiCase AF: 0.940

EpiControl AF: 0.942

ClinVar

ClinVar submissions

Significance: 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	0.061
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.39
DANN	Benign	0.86
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	7.4e-7	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.090
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.041
MPC		0.83
ClinPred		0.0080	T
GERP RS		-8.9
gMVP		0.22
Mutation Taster		=99/1	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: rs3130062; hg19: chr6-31525912;