1-24157659-T-C

Position:

• chr1-24157659-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170743.4(IFNLR1):​c.1034A>G​(p.Glu345Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFNLR1 NM_170743.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062467307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFNLR1	NM_170743.4	c.1034A>G	p.Glu345Gly	missense_variant	7/7	ENST00000327535.6
LOC124903879	XR_007065544.1	n.892T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFNLR1	ENST00000327535.6	c.1034A>G	p.Glu345Gly	missense_variant	7/7	1	NM_170743.4	P1
IFNLR1	ENST00000374421.7	c.947A>G	p.Glu316Gly	missense_variant	7/7	1
IFNLR1	ENST00000327575.6	c.*168A>G		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.1034A>G (p.E345G) alteration is located in exon 7 (coding exon 7) of the IFNLR1 gene. This alteration results from a A to G substitution at nucleotide position 1034, causing the glutamic acid (E) at amino acid position 345 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.12
Sift	Benign	0.087	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0030	B;B
Vest4		0.089
MutPred		0.33		Loss of stability (P = 0.0776);.;
MVP		0.20
MPC		0.27
ClinPred		0.070	T
GERP RS		-1.5
Varity_R		0.070
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-24484149;