rs11249006

Positions:

• chr1-24155984-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.*1146C>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 0.305 in 151,946 control chromosomes in the GnomAD database, including 7,687 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 0.31 (7685 hom., cov: 32)
  • Exomes 𝑓: 0.39 (2 hom.)
• Consequence: IFNLR1 NM_170743.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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 (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNLR1	NM_170743.4	c.*1146C>T		3_prime_UTR_variant	7/7	ENST00000327535.6
LOC124903879	XR_007065544.1	n.487+792G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNLR1	ENST00000327535.6	c.*1146C>T		3_prime_UTR_variant	7/7	1	NM_170743.4	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46367 AN: 151810 Hom.: 7677 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.305 AC: 46410 AN: 151928 Hom.: 7685 Cov.: 32 AF XY: 0.306 AC XY: 22723 AN XY: 74236

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.288

Alfa AF: 0.315 Hom.: 6506

Bravo AF: 0.308

Asia WGS AF: 0.496 AC: 1725 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	2.5
DANN	Benign	0.46

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: rs11249006; hg19: chr1-24482474; COSMIC: COSV59525590; COSMIC: COSV59525590;