rs201104473

Variant names:

• chr19-39243672-C-G
• rs201104473
• NM_172139.4:c.551G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-39243672-C-G
• chr19-39243672-C-T

Variant summary

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

The NM_172139.4(IFNL3):​c.551G>C​(p.Arg184Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,722 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R184Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFNL3 NM_172139.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL3	NM_172139.4	c.551G>C	p.Arg184Pro	missense_variant	Exon 5 of 5	ENST00000413851.3	NP_742151.2
IFNL3	NM_001346937.2	c.563G>C	p.Arg188Pro	missense_variant	Exon 6 of 6		NP_001333866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL3	ENST00000413851.3	c.551G>C	p.Arg184Pro	missense_variant	Exon 5 of 5	1	NM_172139.4	ENSP00000409000.2
IFNL3	ENST00000613087.5	c.563G>C	p.Arg188Pro	missense_variant	Exon 6 of 6	1		ENSP00000481633.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000427 AC: 1 AN: 234220 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000950

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453722 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722554

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.089	.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.2	.;D
REVEL	Benign	0.16
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.99	.;D
Vest4		0.57
MutPred		0.49		.;Loss of helix (P = 0.0626);
MVP		0.37
MPC		0.86
ClinPred		0.98	D
GERP RS		-4.5
Varity_R		0.84
gMVP		0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs201104473; hg19: chr19-39734312;