chr1-67313993-A-T

Variant names:

• chr1-67313993-A-T
• rs10489627
• NM_001374259.2:c.-44A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001374259.2(IL12RB2):​c.-44A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: IL12RB2 NM_001374259.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 15 publications found

Genes affected

IL12RB2 (HGNC:5972): (interleukin 12 receptor subunit beta 2) The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374259.2. 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
	IL12RB2	NM_001374259.2	MANE Select	c.-44A>T		5_prime_UTR	Exon 2 of 17	NP_001361188.1	Q99665-1
	IL12RB2	NM_001258214.1		c.-44A>T		5_prime_UTR	Exon 2 of 16	NP_001245143.1	B4DGA4
	IL12RB2	NM_001319233.1		c.-40A>T		5_prime_UTR	Exon 2 of 16	NP_001306162.1	B4DGA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.-44A>T		5_prime_UTR	Exon 2 of 17	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000541374.6	TSL:1	c.-44A>T		5_prime_UTR	Exon 2 of 13	ENSP00000445276.3	A0A0A0MTN7
	IL12RB2	ENST00000262345.5	TSL:1	c.-37+6026A>T		intron	N/A	ENSP00000262345.1	Q99665-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 17086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.85
PhyloP100		-0.84

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10489627;

hg19: chr1-67779676;