rs12028945

Positions:

• chr1-24155514-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNLR1	NM_170743.4	c.*1616C>T		3_prime_UTR_variant	7/7	ENST00000327535.6
LOC124903879	XR_007065544.1	n.487+322G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNLR1	ENST00000327535.6	c.*1616C>T		3_prime_UTR_variant	7/7	1	NM_170743.4	P1

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0966

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.104 Hom.: 1123

Bravo AF: 0.0766

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.088
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs12028945; hg19: chr1-24482004;