chr19-14039615-A-C

Variant names:

• chr19-14039615-A-C
• rs758946711
• NM_004843.4:c.326A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004843.4(IL27RA):​c.326A>C​(p.Lys109Thr) variant causes a missense 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. 17/22 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. K109R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL27RA NM_004843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 0 publications found

Genes affected

IL27RA (HGNC:17290): (interleukin 27 receptor subunit alpha) In mice, CD4+ helper T-cells differentiate into type 1 (Th1) cells, which are critical for cell-mediated immunity, predominantly under the influence of IL12. Also, IL4 influences their differentiation into type 2 (Th2) cells, which are critical for most antibody responses. Mice deficient in these cytokines, their receptors, or associated transcription factors have impaired, but are not absent of, Th1 or Th2 immune responses. This gene encodes a protein which is similar to the mouse T-cell cytokine receptor Tccr at the amino acid level, and is predicted to be a glycosylated transmembrane protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.122148216).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004843.4. 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
	IL27RA	NM_004843.4	MANE Select	c.326A>C	p.Lys109Thr	missense	Exon 3 of 14	NP_004834.1	Q6UWB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL27RA	ENST00000263379.4	TSL:1 MANE Select	c.326A>C	p.Lys109Thr	missense	Exon 3 of 14	ENSP00000263379.1	Q6UWB1
	IL27RA	ENST00000917021.1		c.326A>C	p.Lys109Thr	missense	Exon 3 of 14	ENSP00000587080.1
	IL27RA	ENST00000855328.1		c.326A>C	p.Lys109Thr	missense	Exon 3 of 14	ENSP00000525387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.2
DANN	Benign	0.96
DEOGEN2	Benign	0.072	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.27
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.11
Sift	Benign	0.055	T
Sift4G	Uncertain	0.024	D
Polyphen		0.24	B
Vest4		0.27
MutPred		0.51		Gain of sheet (P = 0.0101)
MVP		0.14
MPC		0.22
ClinPred		0.10	T
GERP RS		-3.6
Varity_R		0.053
gMVP		0.34
Mutation Taster		=97/3	polymorphism

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: rs758946711; hg19: chr19-14150427;