22-49997051-A-T

Variant names:

• chr22-49997051-A-T
• NM_001371417.1:c.1281T>A
• IL17REL p.Ala427Ala

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001371416.1(IL17REL):​c.1214T>A​(p.Leu405His) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL17REL NM_001371416.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03815502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371416.1. 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.1281T>A	p.Ala427Ala	synonymous	Exon 14 of 15	NP_001358346.1	Q6ZVW7-1
	IL17REL	NM_001371416.1		c.1214T>A	p.Leu405His	missense	Exon 14 of 15	NP_001358345.1	A0A8Q3WLX3
	IL17REL	NM_001001694.3		c.998T>A	p.Leu333His	missense	Exon 14 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.1281T>A	p.Ala427Ala	synonymous	Exon 14 of 15	ENSP00000512282.1	Q6ZVW7-1
	IL17REL	ENST00000695951.1		c.1214T>A	p.Leu405His	missense	Exon 14 of 15	ENSP00000512283.1	A0A8Q3WLX3
	IL17REL	ENST00000389983.7	TSL:2	n.*1133T>A		non_coding_transcript_exon	Exon 14 of 15	ENSP00000374633.3	A0AAA9X3B1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1407870 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 697262

African (AFR) AF: 0.00 AC: 0 AN: 31196

American (AMR) AF: 0.00 AC: 0 AN: 30804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23660

East Asian (EAS) AF: 0.00 AC: 0 AN: 38776

South Asian (SAS) AF: 0.00 AC: 0 AN: 77526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091178

Other (OTH) AF: 0.00 AC: 0 AN: 58184

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.10
DANN	Benign	0.53
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-4.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.016
Sift	Benign	0.033	D
Sift4G	Benign	0.30	T
Varity_R		0.051
gMVP		0.49
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-50435480;