Variant 1-24157624-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_170743.4(IFNLR1):c.1069C>T(p.Pro357Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

IFNLR1
NM_170743.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0290

Variant links:

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]

IFNLR1 links:

LOC124903879 (HGNC:):

LOC124903879 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.069624335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNLR1	NM_170743.4 linkuse as main transcript	c.1069C>T	p.Pro357Ser	missense_variant	7/7	ENST00000327535.6	NP_734464.1	Q8IU57-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IFNLR1	ENST00000327535.6 linkuse as main transcript	c.1069C>T	p.Pro357Ser	missense_variant	7/7	1	NM_170743.4	ENSP00000327824.1	Q8IU57-1
IFNLR1	ENST00000374421.7 linkuse as main transcript	c.982C>T	p.Pro328Ser	missense_variant	7/7	1		ENSP00000363542.3	Q8IU57-2
IFNLR1	ENST00000327575 linkuse as main transcript	c.*203C>T		3_prime_UTR_variant	6/6	1		ENSP00000328994.2	Q8IU57-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244586

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132030

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455256

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.1069C>T (p.P357S) alteration is located in exon 7 (coding exon 7) of the IFNLR1 gene. This alteration results from a C to T substitution at nucleotide position 1069, causing the proline (P) at amino acid position 357 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.9

DANN

Benign

0.43

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.087

Sift

Benign

0.22

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.013

B;B

Vest4

0.035

MutPred

0.087

Gain of glycosylation at P357 (P = 0.0329);.;

MVP

0.15

MPC

0.24

ClinPred

0.033

GERP RS

-0.82

Varity_R

0.034

gMVP

0.098

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over