dbSNP rs567952756: NFKBID:p.Arg383Pro (chr19-35890405-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032721.3(NFKBID):c.1148G>C(p.Arg383Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NFKBID
NM_032721.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.194

Variant links:

Genes affected

NFKBID (HGNC:15671): (NFKB inhibitor delta) Predicted to enable NF-kappaB binding activity. Predicted to be involved in T cell receptor signaling pathway; positive regulation of T-helper 17 cell differentiation; and regulation of gene expression. Predicted to act upstream of or within several processes, including negative regulation of NF-kappaB transcription factor activity; negative regulation of T cell differentiation in thymus; and positive regulation of thymocyte apoptotic process. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NFKBID links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1125851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
NFKBID	NM_032721.3 link	c.1148G>C	p.Arg383Pro	missense_variant	Exon 10 of 12	NP_116110.2
NFKBID	NM_139239.5 link	c.1118G>C	p.Arg373Pro	missense_variant	Exon 10 of 12	NP_640332.2	Q8NI38-1
NFKBID	NM_001321831.2 link	c.737G>C	p.Arg246Pro	missense_variant	Exon 10 of 12	NP_001308760.1
NFKBID	NM_001365705.1 link	c.692G>C	p.Arg231Pro	missense_variant	Exon 10 of 12	NP_001352634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBID	ENST00000641389.3 link	c.1118G>C	p.Arg373Pro	missense_variant	Exon 10 of 12			ENSP00000493265.2		A0A286YF31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249432

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135374

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

.;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.40

.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

.;N;.

REVEL

Benign

0.094

Sift

Benign

0.042

.;D;.

Sift4G

Benign

0.26

.;T;.

Polyphen

0.20, 0.17

.;B;B

Vest4

0.43

MutPred

0.57

.;Gain of catalytic residue at P230 (P = 0.0133);.;

MVP

0.33

MPC

1.9

ClinPred

0.29

GERP RS

1.1

Varity_R

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over