19-39245004-C-G

Variant names:

• chr19-39245004-C-G
• rs28416813
• NM_172139.4:c.-37G>C

Variant summary

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

The NM_172139.4(IFNL3):​c.-37G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,609,610 control chromosomes in the GnomAD database, including 83,364 homozygotes. 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: 𝑓 0.38 (12797 hom., cov: 30)
  • Exomes 𝑓: 0.30 (70567 hom.)
• Consequence: IFNL3 NM_172139.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 45 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172139.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL3	NM_172139.4	MANE Select	c.-37G>C		5_prime_UTR	Exon 1 of 5	NP_742151.2
	IFNL3	NM_001346937.2		c.11-35G>C		intron	N/A	NP_001333866.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNL3	ENST00000413851.3	TSL:1 MANE Select	c.-37G>C		5_prime_UTR	Exon 1 of 5	ENSP00000409000.2
	IFNL3	ENST00000613087.5	TSL:1	c.11-35G>C		intron	N/A	ENSP00000481633.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 57878 AN: 151080 Hom.: 12765 Cov.: 30

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.366

GnomAD2 exomes AF: 0.313 AC: 77750 AN: 248662 AF XY: 0.301

Gnomad AFR exome AF: 0.610

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.0655

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.302 AC: 440284 AN: 1458410 Hom.: 70567 Cov.: 38 AF XY: 0.299 AC XY: 216694 AN XY: 725418

African (AFR) AF: 0.610 AC: 20012 AN: 32788

American (AMR) AF: 0.414 AC: 18380 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 9795 AN: 26002

East Asian (EAS) AF: 0.0804 AC: 3189 AN: 39688

South Asian (SAS) AF: 0.224 AC: 19244 AN: 86004

European-Finnish (FIN) AF: 0.250 AC: 13359 AN: 53358

Middle Eastern (MID) AF: 0.295 AC: 1686 AN: 5718

European-Non Finnish (NFE) AF: 0.303 AC: 336503 AN: 1110226

Other (OTH) AF: 0.301 AC: 18116 AN: 60186

GnomAD4 genome AF: 0.383 AC: 57958 AN: 151200 Hom.: 12797 Cov.: 30 AF XY: 0.374 AC XY: 27628 AN XY: 73898

African (AFR) AF: 0.605 AC: 24666 AN: 40800

American (AMR) AF: 0.371 AC: 5653 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3466

East Asian (EAS) AF: 0.0709 AC: 367 AN: 5174

South Asian (SAS) AF: 0.218 AC: 1047 AN: 4806

European-Finnish (FIN) AF: 0.236 AC: 2502 AN: 10580

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21206 AN: 67858

Other (OTH) AF: 0.362 AC: 757 AN: 2094

Alfa AF: 0.360 Hom.: 1884

Bravo AF: 0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.41
PhyloP100		0.44
PromoterAI		-0.0038	Neutral
Mutation Taster		=300/0	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: rs28416813; hg19: chr19-39735644; COSMIC: COSV69829814; COSMIC: COSV69829814;