rs30461

Variant names:

• chr19-39298475-A-G
• rs30461
• NM_172140.2:c.562A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172140.2(IFNL1):​c.562A>G​(p.Asn188Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,802 control chromosomes in the GnomAD database, including 23,540 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.24 (8660 hom., cov: 31)
  • Exomes 𝑓: 0.11 (14880 hom.)
• Consequence: IFNL1 NM_172140.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 44 publications found

Genes affected

IFNL1 (HGNC:18363): (interferon lambda 1) This gene encodes a cytokine distantly related to type I interferons and the IL-10 family. This gene, interleukin 28A (IL28A), and interleukin 28B (IL28B) 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.621654E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFNL1	NM_172140.2	c.562A>G	p.Asn188Asp	missense_variant	Exon 5 of 5	ENST00000333625.3	NP_742152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFNL1	ENST00000333625.3	c.562A>G	p.Asn188Asp	missense_variant	Exon 5 of 5	1	NM_172140.2	ENSP00000329991.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37053 AN: 151894 Hom.: 8618 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0361

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.127 AC: 32013 AN: 251486 AF XY: 0.118

Gnomad AFR exome AF: 0.631

Gnomad AMR exome AF: 0.0907

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.0409

Gnomad FIN exome AF: 0.0667

Gnomad NFE exome AF: 0.0997

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.114 AC: 166169 AN: 1461790 Hom.: 14880 Cov.: 32 AF XY: 0.111 AC XY: 80766 AN XY: 727204

African (AFR) AF: 0.644 AC: 21552 AN: 33474

American (AMR) AF: 0.0967 AC: 4323 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4305 AN: 26134

East Asian (EAS) AF: 0.0356 AC: 1413 AN: 39700

South Asian (SAS) AF: 0.0841 AC: 7250 AN: 86256

European-Finnish (FIN) AF: 0.0694 AC: 3708 AN: 53418

Middle Eastern (MID) AF: 0.159 AC: 917 AN: 5768

European-Non Finnish (NFE) AF: 0.103 AC: 114382 AN: 1111922

Other (OTH) AF: 0.138 AC: 8319 AN: 60394

GnomAD4 genome AF: 0.244 AC: 37155 AN: 152012 Hom.: 8660 Cov.: 31 AF XY: 0.237 AC XY: 17642 AN XY: 74332

African (AFR) AF: 0.617 AC: 25565 AN: 41424

American (AMR) AF: 0.145 AC: 2213 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3466

East Asian (EAS) AF: 0.0364 AC: 188 AN: 5164

South Asian (SAS) AF: 0.0854 AC: 412 AN: 4822

European-Finnish (FIN) AF: 0.0742 AC: 786 AN: 10600

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.101 AC: 6849 AN: 67956

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.139 Hom.: 13861

Bravo AF: 0.268

TwinsUK AF: 0.0949 AC: 352

ALSPAC AF: 0.104 AC: 399

ESP6500AA AF: 0.620 AC: 2730

ESP6500EA AF: 0.106 AC: 912

ExAC AF: 0.136 AC: 16539

Asia WGS AF: 0.110 AC: 386 AN: 3478

EpiCase AF: 0.105

EpiControl AF: 0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.47
DANN	Benign	0.13
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00012	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000036	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.64
PrimateAI	Benign	0.31	T
PROVEAN	Benign	3.5	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.080
ClinPred		0.00058	T
GERP RS		1.2
Varity_R		0.082
gMVP		0.025
Mutation Taster		=98/2	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: rs30461; hg19: chr19-39789115; COSMIC: COSV61318113;