rs12028945

Variant names:

• chr1-24155514-G-A
• rs12028945
• NM_170743.4:c.*1616C>T

Variant summary

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

The NM_170743.4(IFNLR1):​c.*1616C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,274 control chromosomes in the GnomAD database, including 652 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 0.080 (652 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFNLR1 NM_170743.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 8 publications found

Genes affected

IFNLR1 (HGNC:18584): (interferon lambda receptor 1) The protein encoded by this gene belongs to the class II cytokine receptor family. This protein forms a receptor complex with interleukine 10 receptor, beta (IL10RB). The receptor complex has been shown to interact with three closely related cytokines, including interleukin 28A (IL28A), interleukin 28B (IL28B), and interleukin 29 (IL29). The expression of all three cytokines can be induced by viral infection. The cells overexpressing this protein have been found to have enhanced responses to IL28A and IL29, but decreased response to IL28B. Three alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

LOC124903879 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170743.4. 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
	IFNLR1	NM_170743.4	MANE Select	c.*1616C>T		3_prime_UTR	Exon 7 of 7	NP_734464.1	Q8IU57-1
	IFNLR1	NM_173064.3		c.*1616C>T		3_prime_UTR	Exon 7 of 7	NP_775087.1	Q8IU57-2
	IFNLR1	NM_173065.3		c.*2313C>T		3_prime_UTR	Exon 6 of 6	NP_775088.1	Q8IU57-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNLR1	ENST00000327535.6	TSL:1 MANE Select	c.*1616C>T		3_prime_UTR	Exon 7 of 7	ENSP00000327824.1	Q8IU57-1
	IFNLR1	ENST00000923176.1		c.*1616C>T		3_prime_UTR	Exon 5 of 5	ENSP00000593235.1
	IFNLR1	ENST00000873466.1		c.*1616C>T		3_prime_UTR	Exon 5 of 5	ENSP00000543525.1

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12217 AN: 152156 Hom.: 652 Cov.: 33

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0789

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0802 AC: 12210 AN: 152274 Hom.: 652 Cov.: 33 AF XY: 0.0807 AC XY: 6007 AN XY: 74458

African (AFR) AF: 0.0244 AC: 1016 AN: 41566

American (AMR) AF: 0.0758 AC: 1160 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 335 AN: 3468

East Asian (EAS) AF: 0.154 AC: 797 AN: 5176

South Asian (SAS) AF: 0.158 AC: 764 AN: 4822

European-Finnish (FIN) AF: 0.0607 AC: 644 AN: 10614

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7232 AN: 68014

Other (OTH) AF: 0.0776 AC: 164 AN: 2114

Alfa AF: 0.101 Hom.: 1352

Bravo AF: 0.0766

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.088
DANN	Benign	0.53
PhyloP100		-1.2
Mutation Taster		=100/0	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: rs12028945; hg19: chr1-24482004;