Variant chr1-24157153-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_170743.4(IFNLR1):c.1540T>C(p.Leu514=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 1,612,476 control chromosomes in the GnomAD database, including 643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 248 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 395 hom. )

Consequence

IFNLR1
NM_170743.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-24157153-A-G is Benign according to our data. Variant chr1-24157153-A-G is described in ClinVar as [Benign]. Clinvar id is 3056961.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNLR1	NM_170743.4 linkuse as main transcript	c.1540T>C	p.Leu514=	synonymous_variant	7/7	ENST00000327535.6
LOC124903879	XR_007065544.1 linkuse as main transcript	n.488-102A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNLR1	ENST00000327535.6 linkuse as main transcript	c.1540T>C	p.Leu514=	synonymous_variant	7/7	1	NM_170743.4	P1	Q8IU57-1
IFNLR1	ENST00000374421.7 linkuse as main transcript	c.1453T>C	p.Leu485=	synonymous_variant	7/7	1			Q8IU57-2
IFNLR1	ENST00000327575.6 linkuse as main transcript	c.*674T>C		3_prime_UTR_variant	6/6	1			Q8IU57-4

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5101

AN:

152066

Hom.:

247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00174

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0137

AC:

3433

AN:

250030

Hom.:

144

AF XY:

0.0131

AC XY:

1774

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.00523

Gnomad ASJ exome

AF:

0.000303

Gnomad EAS exome

AF:

0.00185

Gnomad SAS exome

AF:

0.0400

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000920

Gnomad OTH exome

AF:

0.00623

GnomAD4 exome

AF:

0.00608

AC:

8882

AN:

1460292

Hom.:

395

Cov.:

AF XY:

0.00668

AC XY:

4852

AN XY:

726454

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.00587

Gnomad4 ASJ exome

AF:

0.000423

Gnomad4 EAS exome

AF:

0.000730

Gnomad4 SAS exome

AF:

0.0393

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000408

Gnomad4 OTH exome

AF:

0.00972

GnomAD4 genome

AF:

0.0336

AC:

5115

AN:

152184

Hom.:

248

Cov.:

AF XY:

0.0334

AC XY:

2488

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.0352

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

IFNLR1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.2

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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