rs10903035

Positions:

• chr1-24155450-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000327535.6(IFNLR1):​c.*1680C>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 0.626 in 152,038 control chromosomes in the GnomAD database, including 30,061 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 0.63 (30053 hom., cov: 32)
  • Exomes 𝑓: 0.60 (8 hom.)
• Consequence: IFNLR1 ENST00000327535.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNLR1	NM_170743.4	c.*1680C>T		3_prime_UTR_variant	7/7	ENST00000327535.6	NP_734464.1
LOC124903879	XR_007065544.1	n.487+258G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNLR1	ENST00000327535.6	c.*1680C>T		3_prime_UTR_variant	7/7	1	NM_170743.4	ENSP00000327824	P1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95128 AN: 151890 Hom.: 30040 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.600 AC: 18 AN: 30 Hom.: 8 Cov.: 0 AF XY: 0.450 AC XY: 9 AN XY: 20

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.626 AC: 95173 AN: 152008 Hom.: 30053 Cov.: 32 AF XY: 0.629 AC XY: 46758 AN XY: 74298

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.650

Alfa AF: 0.651 Hom.: 31947

Bravo AF: 0.615

Asia WGS AF: 0.591 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.98
DANN	Benign	0.45

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: rs10903035; hg19: chr1-24481940;