rs1467183972

Variant names:

• chr19-35888587-C-A
• ENST00000606253.5:c.1370G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-35888587-C-A
• chr19-35888587-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032721.3(NFKBID):​c.1370G>T​(p.Arg457Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NFKBID NM_032721.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27087337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFKBID	NM_032721.3	c.1370G>T	p.Arg457Leu	missense_variant	Exon 12 of 12		NP_116110.2
NFKBID	NM_139239.5	c.1340G>T	p.Arg447Leu	missense_variant	Exon 12 of 12		NP_640332.2
NFKBID	NM_001321831.2	c.959G>T	p.Arg320Leu	missense_variant	Exon 12 of 12		NP_001308760.1
NFKBID	NM_001365705.1	c.914G>T	p.Arg305Leu	missense_variant	Exon 12 of 12		NP_001352634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFKBID	ENST00000641389.3	c.1340G>T	p.Arg447Leu	missense_variant	Exon 12 of 12			ENSP00000493265.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420210 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702898

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: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	.;N;.
REVEL	Benign	0.13
Sift	Benign	0.041	.;D;.
Sift4G	Uncertain	0.018	.;D;.
Polyphen		0.99, 1.0	.;D;D
Vest4		0.52
MutPred		0.39		.;Loss of MoRF binding (P = 2e-04);.;
MVP		0.51
MPC		1.8
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36379489;