rs1394467999

Variant names:

• chr22-49997703-C-A
• rs1394467999
• NM_001371417.1:c.1075G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-49997703-C-A
• chr22-49997703-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001371417.1(IL17REL):​c.1075G>T​(p.Glu359*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IL17REL NM_001371417.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.53
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371417.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17REL	NM_001371417.1	MANE Select	c.1075G>T	p.Glu359*	stop_gained	Exon 12 of 15	NP_001358346.1	Q6ZVW7-1
	IL17REL	NM_001371416.1		c.1075G>T	p.Glu359*	stop_gained	Exon 12 of 15	NP_001358345.1	A0A8Q3WLX3
	IL17REL	NM_001001694.3		c.859G>T	p.Glu287*	stop_gained	Exon 12 of 15	NP_001001694.2	Q6ZVW7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17REL	ENST00000695950.1	MANE Select	c.1075G>T	p.Glu359*	stop_gained	Exon 12 of 15	ENSP00000512282.1	Q6ZVW7-1
	IL17REL	ENST00000695951.1		c.1075G>T	p.Glu359*	stop_gained	Exon 12 of 15	ENSP00000512283.1	A0A8Q3WLX3
	IL17REL	ENST00000389983.7	TSL:2	n.*994G>T		non_coding_transcript_exon	Exon 12 of 15	ENSP00000374633.3	A0AAA9X3B1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461596 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Benign	0.93
Eigen	Benign	-0.57
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0050	N
PhyloP100		-4.5
Vest4		0.12
GERP RS		-3.5
Mutation Taster		=117/83	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1394467999; hg19: chr22-50436132;