rs201418207

Variant names:

• chr19-39244460-C-G
• rs201418207
• NM_172139.4:c.215G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-39244460-C-G
• chr19-39244460-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172139.4(IFNL3):​c.215G>C​(p.Arg72Pro) 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. 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. R72H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNL3 NM_172139.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

IFNL3 (HGNC:18365): (interferon lambda 3) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 29 (IL29) are three closely related cytokine genes that form a cytokine gene cluster on a chromosomal region mapped to 19q13. Expression of the cytokines encoded by the three genes can be induced by viral infection. All three cytokines have been shown to interact with a heterodimeric class II cytokine receptor that consists of interleukin 10 receptor, beta (IL10RB) and interleukin 28 receptor, alpha (IL28RA). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06986183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL3	NM_172139.4	c.215G>C	p.Arg72Pro	missense_variant	Exon 2 of 5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2	c.227G>C	p.Arg76Pro	missense_variant	Exon 3 of 6		NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3	c.215G>C	p.Arg72Pro	missense_variant	Exon 2 of 5	1	NM_172139.4	ENSP00000409000.2
IFNL3	ENST00000613087.5	c.227G>C	p.Arg76Pro	missense_variant	Exon 3 of 6	1		ENSP00000481633.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458218 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725298

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.8
DANN	Benign	0.92
DEOGEN2	Benign	0.0087	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.045	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	.;N
REVEL	Benign	0.040
Sift	Benign	0.23	.;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0040	.;B
Vest4		0.14
MutPred		0.24		.;Loss of MoRF binding (P = 0.0104);
MVP		0.14
MPC		0.29
ClinPred		0.21	T
GERP RS		-3.4
Varity_R		0.56
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs201418207; hg19: chr19-39735100;