Genetic Variant NM_001371417.1:c.1064G>A (chr22-49997714-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001371417.1(IL17REL):c.1064G>A(p.Arg355Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,613,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

IL17REL
NM_001371417.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

5 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12460306).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL17REL	NM_001371417.1	MANE Select	c.1064G>A	p.Arg355Gln	missense	Exon 12 of 15	NP_001358346.1	Q6ZVW7-1
IL17REL	NM_001371416.1		c.1064G>A	p.Arg355Gln	missense	Exon 12 of 15	NP_001358345.1	A0A8Q3WLX3
IL17REL	NM_001001694.3		c.848G>A	p.Arg283Gln	missense	Exon 12 of 15	NP_001001694.2	Q6ZVW7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL17REL	ENST00000695950.1	MANE Select	c.1064G>A	p.Arg355Gln	missense	Exon 12 of 15	ENSP00000512282.1	Q6ZVW7-1
IL17REL	ENST00000695951.1		c.1064G>A	p.Arg355Gln	missense	Exon 12 of 15	ENSP00000512283.1	A0A8Q3WLX3
IL17REL	ENST00000389983.7	TSL:2	n.*983G>A		non_coding_transcript_exon	Exon 12 of 15	ENSP00000374633.3	A0AAA9X3B1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000227

AC:

AN:

250996

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000284

AC:

415

AN:

1461608

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

211

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000733

AC:

AN:

53192

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000324

AC:

360

AN:

1111970

Other (OTH)

AF:

0.0000994

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68018

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000228

Hom.:

Bravo

AF:

0.000159

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.68

M_CAP

Benign

0.0036

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

1.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.99

REVEL

Benign

0.044

Sift

Benign

0.030

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.27

MVP

0.20

MPC

0.62

ClinPred

0.14

GERP RS

0.0049

Varity_R

0.081

gMVP

0.41

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over