Genetic Variant NM_005007.4:c.378C>T (chr6-31557671-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_005007.4(NFKBIL1):c.378C>T(p.Ser126Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,575,870 control chromosomes in the GnomAD database, including 19,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1585 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17953 hom. )

Consequence

NFKBIL1
NM_005007.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.723

Variant links:

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]

NFKBIL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 6-31557671-C-T is Benign according to our data. Variant chr6-31557671-C-T is described in ClinVar as [Benign]. Clinvar id is 3060308.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.723 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBIL1	NM_005007.4 link	c.378C>T	p.Ser126Ser	synonymous_variant	Exon 3 of 4	ENST00000376148.9	NP_004998.3	Q9UBC1-1A8K778
NFKBIL1	NM_001144961.2 link	c.378C>T	p.Ser126Ser	synonymous_variant	Exon 3 of 4		NP_001138433.1	Q9UBC1-3A0A0A0MRT5A8K778
NFKBIL1	NM_001144962.2 link	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 4		NP_001138434.1	Q9UBC1-2Q5STV6
NFKBIL1	NM_001144963.2 link	c.309C>T	p.Ser103Ser	synonymous_variant	Exon 3 of 4		NP_001138435.1	Q9UBC1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBIL1	ENST00000376148.9 link	c.378C>T	p.Ser126Ser	synonymous_variant	Exon 3 of 4	1	NM_005007.4	ENSP00000365318.4		Q9UBC1-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20002

AN:

151982

Hom.:

1587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.144

GnomAD3 exomes

AF:

0.163

AC:

38474

AN:

236606

Hom.:

3369

AF XY:

0.169

AC XY:

21639

AN XY:

128228

show subpopulations

Gnomad AFR exome

AF:

0.0574

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.192

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.154

AC:

218556

AN:

1423770

Hom.:

17953

Cov.:

AF XY:

0.157

AC XY:

110221

AN XY:

702874

show subpopulations

Gnomad4 AFR exome

AF:

0.0580

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.132

AC:

20012

AN:

152100

Hom.:

1585

Cov.:

AF XY:

0.136

AC XY:

10083

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.180

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.156

Hom.:

3655

Bravo

AF:

0.123

Asia WGS

AF:

0.206

AC:

717

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NFKBIL1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.7

DANN

Benign

0.68

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over