NM_014438.5:c.261+789T>C

Variant names:

• chr2-113028150-A-G
• rs1562304
• NM_014438.5:c.261+789T>C

Variant summary

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

The NM_014438.5(IL36B):​c.261+789T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 1,571,238 control chromosomes in the GnomAD database, including 689,444 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 0.95 (69253 hom., cov: 30)
  • Exomes 𝑓: 0.93 (620191 hom.)
• Consequence: IL36B NM_014438.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 8 publications found

Genes affected

IL36B (HGNC:15564): (interleukin 36 beta) The protein encoded by this gene is a member of the interleukin 1 cytokine family. Protein structure modeling indicated that this cytokine may contain a 12-stranded beta-trefoil structure that is conserved between IL1A (IL-A alpha) and IL1B (IL-1 beta). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL36B	NM_014438.5	c.261+789T>C		intron_variant	Intron 4 of 5	ENST00000259213.9	NP_055253.2
IL36B	NM_173178.3	c.262-35T>C		intron_variant	Intron 4 of 4		NP_775270.1
IL36B	XM_011510962.1	c.262-35T>C		intron_variant	Intron 4 of 4		XP_011509264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL36B	ENST00000259213.9	c.261+789T>C		intron_variant	Intron 4 of 5	1	NM_014438.5	ENSP00000259213.4
IL36B	ENST00000327407.2	c.262-35T>C		intron_variant	Intron 4 of 4	1		ENSP00000328420.2

Frequencies

GnomAD3 genomes AF: 0.953 AC: 145010 AN: 152100 Hom.: 69193 Cov.: 30

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.964

GnomAD2 exomes AF: 0.954 AC: 236351 AN: 247658 AF XY: 0.954

Gnomad AFR exome AF: 0.988

Gnomad AMR exome AF: 0.977

Gnomad ASJ exome AF: 0.977

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.933

Gnomad NFE exome AF: 0.928

Gnomad OTH exome AF: 0.953

GnomAD4 exome AF: 0.935 AC: 1326194 AN: 1419020 Hom.: 620191 Cov.: 24 AF XY: 0.936 AC XY: 663249 AN XY: 708790

African (AFR) AF: 0.990 AC: 32107 AN: 32424

American (AMR) AF: 0.976 AC: 43389 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 25226 AN: 25816

East Asian (EAS) AF: 1.00 AC: 39463 AN: 39468

South Asian (SAS) AF: 0.986 AC: 84206 AN: 85406

European-Finnish (FIN) AF: 0.934 AC: 49786 AN: 53286

Middle Eastern (MID) AF: 0.992 AC: 5604 AN: 5652

European-Non Finnish (NFE) AF: 0.923 AC: 990957 AN: 1073690

Other (OTH) AF: 0.943 AC: 55456 AN: 58826

GnomAD4 genome AF: 0.953 AC: 145129 AN: 152218 Hom.: 69253 Cov.: 30 AF XY: 0.956 AC XY: 71111 AN XY: 74408

African (AFR) AF: 0.987 AC: 40979 AN: 41526

American (AMR) AF: 0.972 AC: 14863 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3397 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5173 AN: 5174

South Asian (SAS) AF: 0.989 AC: 4765 AN: 4816

European-Finnish (FIN) AF: 0.938 AC: 9930 AN: 10586

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62839 AN: 68026

Other (OTH) AF: 0.965 AC: 2039 AN: 2114

Alfa AF: 0.941 Hom.: 13337

Bravo AF: 0.959

Asia WGS AF: 0.997 AC: 3466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.62
PhyloP100		-0.16
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: rs1562304; hg19: chr2-113785727;