dbSNP rs5771069: IL17REL:p.Ala427Ala (chr22-49997051-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001371417.1(IL17REL):c.1281T>C(p.Ala427Ala) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.83

Publications

74 publications found

Variant links:

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]

IL17REL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein
IL17REL	NM_001371417.1 link	c.1281T>C	p.Ala427Ala	synonymous_variant	Exon 14 of 15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1 link	c.1214T>C	p.Leu405Pro	missense_variant	Exon 14 of 15		NP_001358345.1
IL17REL	NM_001001694.3 link	c.998T>C	p.Leu333Pro	missense_variant	Exon 14 of 15		NP_001001694.2
IL17REL	XR_001755245.2 link	n.1400T>C		non_coding_transcript_exon_variant	Exon 14 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
IL17REL	ENST00000695950.1 link	c.1281T>C	p.Ala427Ala	synonymous_variant	Exon 14 of 15		NM_001371417.1	ENSP00000512282.1
IL17REL	ENST00000695951.1 link	c.1214T>C	p.Leu405Pro	missense_variant	Exon 14 of 15			ENSP00000512283.1
IL17REL	ENST00000389983.7 link	n.*1133T>C		non_coding_transcript_exon_variant	Exon 14 of 15	2		ENSP00000374633.3
IL17REL	ENST00000389983.7 link	n.*1133T>C		3_prime_UTR_variant	Exon 14 of 15	2		ENSP00000374633.3

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83926

AN:

151954

Hom.:

23604

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.564

AC:

104593

AN:

185426

AF XY:

0.569

show subpopulations

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 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.:

AF XY:

0.531

AC XY:

370033

AN XY:

696380

show subpopulations

African (AFR)

AF:

0.623

AC:

19402

AN:

31162

American (AMR)

AF:

0.530

AC:

16301

AN:

30732

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

13772

AN:

23642

East Asian (EAS)

AF:

0.532

AC:

20613

AN:

38746

South Asian (SAS)

AF:

0.764

AC:

59140

AN:

77454

European-Finnish (FIN)

AF:

0.579

AC:

29465

AN:

50916

Middle Eastern (MID)

AF:

0.670

AC:

3748

AN:

5592

European-Non Finnish (NFE)

AF:

0.499

AC:

543955

AN:

1089734

Other (OTH)

AF:

0.545

AC:

31668

AN:

58112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

15756

31513

47269

63026

78782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16120

32240

48360

64480

80600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.552

AC:

84008

AN:

152072

Hom.:

23630

Cov.:

AF XY:

0.558

AC XY:

41492

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.616

AC:

25563

AN:

41486

American (AMR)

AF:

0.502

AC:

7678

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2103

AN:

3470

East Asian (EAS)

AF:

0.567

AC:

2930

AN:

5166

South Asian (SAS)

AF:

0.764

AC:

3694

AN:

4834

European-Finnish (FIN)

AF:

0.588

AC:

6225

AN:

10584

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34154

AN:

67932

Other (OTH)

AF:

0.536

AC:

1131

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1987

3973

5960

7946

9933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.522

Hom.:

70844

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

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.00062

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.19

T;.

MetaRNN

Benign

0.0000010

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.20

N;N

PhyloP100

-4.8

PrimateAI

Benign

0.30

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

GERP RS

-4.3

Varity_R

0.030

gMVP

0.54

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over