NM_005007.4:c.335-300T>G

Variant names:

• chr6-31557328-T-G
• rs2857604
• NM_005007.4:c.335-300T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005007.4(NFKBIL1):​c.335-300T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,114 control chromosomes in the GnomAD database, including 3,086 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 0.19 (3086 hom., cov: 30)
• Consequence: NFKBIL1 NM_005007.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4	c.335-300T>G		intron_variant	Intron 2 of 3	ENST00000376148.9	NP_004998.3
NFKBIL1	NM_001144961.2	c.335-300T>G		intron_variant	Intron 2 of 3		NP_001138433.1
NFKBIL1	NM_001144962.2	c.266-300T>G		intron_variant	Intron 2 of 3		NP_001138434.1
NFKBIL1	NM_001144963.2	c.266-300T>G		intron_variant	Intron 2 of 3		NP_001138435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9	c.335-300T>G		intron_variant	Intron 2 of 3	1	NM_005007.4	ENSP00000365318.4

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29471 AN: 151996 Hom.: 3083 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29496 AN: 152114 Hom.: 3086 Cov.: 30 AF XY: 0.192 AC XY: 14241 AN XY: 74348

African (AFR) AF: 0.181 AC: 7491 AN: 41490

American (AMR) AF: 0.284 AC: 4338 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3464

East Asian (EAS) AF: 0.166 AC: 860 AN: 5178

South Asian (SAS) AF: 0.166 AC: 800 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1111 AN: 10592

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.191 AC: 12979 AN: 67974

Other (OTH) AF: 0.223 AC: 470 AN: 2106

Alfa AF: 0.105 Hom.: 405

Bravo AF: 0.211

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2857604; hg19: chr6-31525105;