rs5771069

chr22-49997051-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001371417.1(IL17REL):c.1281T>C(p.Ala427=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,558,162 control chromosomes in the GnomAD database, including 220,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23630 hom., cov: 34)
  • Exomes 𝑓: 0.52 (197210 hom.)
• Consequence: IL17REL NM_001371417.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0144996E-6).
• BP7: Synonymous conserved (PhyloP=-4.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17REL	NM_001371417.1	c.1281T>C	p.Ala427=	synonymous_variant	14/15	ENST00000695950.1
IL17REL	NM_001371416.1	c.1214T>C	p.Leu405Pro	missense_variant	14/15
IL17REL	NM_001001694.3	c.998T>C	p.Leu333Pro	missense_variant	14/15
IL17REL	XR_001755245.2	n.1400T>C		non_coding_transcript_exon_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17REL	ENST00000695950.1	c.1281T>C	p.Ala427=	synonymous_variant	14/15		NM_001371417.1	A2
IL17REL	ENST00000695951.1	c.1214T>C	p.Leu405Pro	missense_variant	14/15			P2
IL17REL	ENST00000389983.7	c.*1133T>C		3_prime_UTR_variant, NMD_transcript_variant	14/15	2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83926 AN: 151954 Hom.: 23604 Cov.: 34

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.535

GnomAD3 exomes AF: 0.564 AC: 104593 AN: 185426 Hom.: 30121 AF XY: 0.569 AC XY: 56978 AN XY: 100172

Gnomad AFR exome AF: 0.615

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.562

Gnomad SAS exome AF: 0.768

Gnomad FIN exome AF: 0.581

Gnomad NFE exome AF: 0.507

Gnomad OTH exome AF: 0.560

GnomAD4 exome AF: 0.525 AC: 738064 AN: 1406090 Hom.: 197210 Cov.: 38 AF XY: 0.531 AC XY: 370033 AN XY: 696380

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.532

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.552 AC: 84008 AN: 152072 Hom.: 23630 Cov.: 34 AF XY: 0.558 AC XY: 41492 AN XY: 74344

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.536

Alfa AF: 0.521 Hom.: 30068

Bravo AF: 0.542

TwinsUK AF: 0.505 AC: 1872

ALSPAC AF: 0.503 AC: 1937

ESP6500AA AF: 0.606 AC: 2651

ESP6500EA AF: 0.502 AC: 4311

ExAC AF: 0.548 AC: 65158

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.11
Dann	Benign	0.62
DEOGEN2	Benign	0.00062	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.19	T;.
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.20	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.0	N;N
REVEL	Benign	0.014
Sift	Benign	0.16	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0	B;B
Vest4		0.027
MPC		0.35
ClinPred		0.0072	T
GERP RS		-4.3
Varity_R		0.030
gMVP		0.54

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

Other links and lift over

dbSNP: rs5771069; hg19: chr22-50435480; COSMIC: COSV105909913;