dbSNP rs372757172: IL36A:p.Thr149Ser (chr2-113008013-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014440.3(IL36A):c.446C>G(p.Thr149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T149I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IL36A
NM_014440.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.64

Variant links:

Genes affected

IL36A (HGNC:15562): (interleukin 36 alpha) The protein encoded by this gene is a cytokine that can activate NF-kappa-B and MAPK signaling pathways to generate an inflammatory response. The encoded protein functions primarily in skin and demonstrates increased expression in psoriasis. In addition, decreased expression of this gene has been linked to a poor prognosis in both hepatocellular carcinoma and colorectal cancer patients. [provided by RefSeq, Nov 2015]

IL36A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0657537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36A	NM_014440.3 link	c.446C>G	p.Thr149Ser	missense_variant	Exon 4 of 4	ENST00000259211.7	NP_055255.1	Q9UHA7
IL36A	XM_005263639.3 link	c.446C>G	p.Thr149Ser	missense_variant	Exon 4 of 5		XP_005263696.1	Q9UHA7
IL36A	XM_011510965.2 link	c.446C>G	p.Thr149Ser	missense_variant	Exon 4 of 5		XP_011509267.1	Q9UHA7
IL36A	XM_017003806.2 link	c.446C>G	p.Thr149Ser	missense_variant	Exon 4 of 5		XP_016859295.1	Q9UHA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36A	ENST00000259211.7 link	c.446C>G	p.Thr149Ser	missense_variant	Exon 4 of 4	1	NM_014440.3	ENSP00000259211.6		Q9UHA7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135346

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727242

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0060

DANN

Benign

0.50

DEOGEN2

Benign

0.0042

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.25

M_CAP

Benign

0.0031

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.84

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.090

REVEL

Benign

0.0070

Sift

Benign

0.63

Sift4G

Benign

0.74

Polyphen

0.22

Vest4

0.036

MutPred

0.45

Gain of disorder (P = 0.0613);

MVP

0.040

MPC

0.078

ClinPred

0.091

GERP RS

-9.3

Varity_R

0.074

gMVP

0.21

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