rs1340182755

Variant names:

• chr22-49997354-C-G
• NM_001371417.1:c.1223G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-49997354-C-G
• chr22-49997354-C-T

Variant summary

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

The NM_001371417.1(IL17REL):​c.1223G>C​(p.Arg408Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R408H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IL17REL NM_001371417.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

Genes affected

IL17REL (HGNC:33808): (interleukin 17 receptor E like) Predicted to enable interleukin-17 receptor activity. Predicted to be involved in cytokine-mediated signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

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=0.042583674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17REL	NM_001371417.1	c.1223G>C	p.Arg408Pro	missense_variant	Exon 13 of 15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1	c.1156G>C	p.Ala386Pro	missense_variant	Exon 13 of 15		NP_001358345.1
IL17REL	NM_001001694.3	c.940G>C	p.Ala314Pro	missense_variant	Exon 13 of 15		NP_001001694.2
IL17REL	XR_001755245.2	n.1342G>C		non_coding_transcript_exon_variant	Exon 13 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17REL	ENST00000695950.1	c.1223G>C	p.Arg408Pro	missense_variant	Exon 13 of 15		NM_001371417.1	ENSP00000512282.1
IL17REL	ENST00000695951.1	c.1156G>C	p.Ala386Pro	missense_variant	Exon 13 of 15			ENSP00000512283.1
IL17REL	ENST00000389983.7	n.*1075G>C		non_coding_transcript_exon_variant	Exon 13 of 15	2		ENSP00000374633.3
IL17REL	ENST00000389983.7	n.*1075G>C		3_prime_UTR_variant	Exon 13 of 15	2		ENSP00000374633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461466 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.71
DANN	Benign	0.44
DEOGEN2	Benign	0.0060	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.21	T;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.041
Sift	Benign	0.36	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0	B;B
Vest4		0.15
MutPred		0.059		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.040
MPC		0.28
ClinPred		0.059	T
GERP RS		-5.8
Varity_R		0.15
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr22-50435783;