Variant 1-24157705-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_170743.4(IFNLR1):c.988G>A(p.Asp330Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 1,613,996 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 6 hom. )

Consequence

IFNLR1
NM_170743.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.05

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003004849).

BP6

Variant 1-24157705-C-T is Benign according to our data. Variant chr1-24157705-C-T is described in ClinVar as [Benign]. Clinvar id is 3035712.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNLR1	NM_170743.4 linkuse as main transcript	c.988G>A	p.Asp330Asn	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.988G>A	p.Asp330Asn	missense_variant	7/7	1	NM_170743.4	ENSP00000327824.1	Q8IU57-1
IFNLR1	ENST00000374421.7 linkuse as main transcript	c.901G>A	p.Asp301Asn	missense_variant	7/7	1		ENSP00000363542.3	Q8IU57-2
IFNLR1	ENST00000327575 linkuse as main transcript	c.*122G>A		3_prime_UTR_variant	6/6	1		ENSP00000328994.2	Q8IU57-4

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

336

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00774

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000574

AC:

144

AN:

251022

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00800

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000233

AC:

341

AN:

1461650

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00878

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00221

AC:

336

AN:

152346

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00772

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.00257

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000675

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IFNLR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 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

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.023

Sift

Benign

0.030

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

0.058

B;B

Vest4

0.12

MVP

0.099

MPC

0.22

ClinPred

0.0049

GERP RS

0.48

Varity_R

0.047

gMVP

0.096

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