NM_002187.3:c.*901delA

Variant names:

• chr5-159315199-AT-A
• rs34324765
• NM_002187.3:c.*901delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002187.3(IL12B):​c.*901delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 147,178 control chromosomes in the GnomAD database, including 1,914 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1914 hom., cov: 29)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: IL12B NM_002187.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.466
• Publications: 1 publications found

Genes affected

IL12B (HGNC:5970): (interleukin 12B) This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008]

IL12B Gene-Disease associations (from GenCC):

• Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

IL12B-AS1 (HGNC:58156):

LOC105377683 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-159315199-AT-A is Benign according to our data. Variant chr5-159315199-AT-A is described in ClinVar as Benign. ClinVar VariationId is 352559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002187.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	NM_002187.3	MANE Select	c.*901delA		3_prime_UTR	Exon 8 of 8	NP_002178.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12B	ENST00000231228.3	TSL:1 MANE Select	c.*901delA		3_prime_UTR	Exon 8 of 8	ENSP00000231228.2	P29460
	IL12B	ENST00000696750.1		c.*901delA		3_prime_UTR	Exon 5 of 5	ENSP00000512849.1	A0A8Q3WML5
	IL12B	ENST00000696751.1		n.*1383delA		non_coding_transcript_exon	Exon 7 of 7	ENSP00000512850.1	A0A8Q3SJ12

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22092 AN: 146968 Hom.: 1899 Cov.: 29

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.100 AC: 13 AN: 130 Hom.: 0 Cov.: 0 AF XY: 0.0952 AC XY: 8 AN XY: 84

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.0638 AC: 6 AN: 94

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.231 AC: 6 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.151 AC: 22139 AN: 147048 Hom.: 1914 Cov.: 29 AF XY: 0.146 AC XY: 10424 AN XY: 71494

African (AFR) AF: 0.246 AC: 9947 AN: 40390

American (AMR) AF: 0.156 AC: 2308 AN: 14754

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 635 AN: 3420

East Asian (EAS) AF: 0.0420 AC: 212 AN: 5050

South Asian (SAS) AF: 0.0683 AC: 315 AN: 4614

European-Finnish (FIN) AF: 0.0813 AC: 748 AN: 9200

Middle Eastern (MID) AF: 0.187 AC: 53 AN: 284

European-Non Finnish (NFE) AF: 0.113 AC: 7511 AN: 66396

Other (OTH) AF: 0.156 AC: 318 AN: 2038

Alfa AF: 0.0450 Hom.: 40

Bravo AF: 0.158

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Familial Atypical Mycobacteriosis, Autosomal Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34324765; hg19: chr5-158742207;