Genetic Variant NM_001371417.1:c.946G>A (chr22-49998181-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001371417.1(IL17REL):c.946G>A(p.Gly316Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,610,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

IL17REL
NM_001371417.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.11

Publications

0 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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023227036).

BP6

Variant 22-49998181-C-T is Benign according to our data. Variant chr22-49998181-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2272813.Status of the report is criteria_provided_single_submitter, 1 stars.

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.946G>A	p.Gly316Ser	missense	Exon 10 of 15	NP_001358346.1	Q6ZVW7-1
IL17REL	NM_001371416.1		c.946G>A	p.Gly316Ser	missense	Exon 10 of 15	NP_001358345.1	A0A8Q3WLX3
IL17REL	NM_001001694.3		c.730G>A	p.Gly244Ser	missense	Exon 10 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.946G>A	p.Gly316Ser	missense	Exon 10 of 15	ENSP00000512282.1	Q6ZVW7-1
IL17REL	ENST00000695951.1		c.946G>A	p.Gly316Ser	missense	Exon 10 of 15	ENSP00000512283.1	A0A8Q3WLX3
IL17REL	ENST00000389983.7	TSL:2	n.*865G>A		non_coding_transcript_exon	Exon 10 of 15	ENSP00000374633.3	A0AAA9X3B1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000419

AC:

AN:

238590

AF XY:

0.0000383

show subpopulations

Gnomad AFR exome

AF:

0.000201

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000954

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1458006

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725316

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33386

American (AMR)

AF:

0.000158

AC:

AN:

44194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1110916

Other (OTH)

AF:

0.0000332

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41460

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

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:

0.000100

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.068

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.066

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.00050

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.32

M_CAP

Benign

0.0013

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

PhyloP100

-2.1

PrimateAI

Benign

0.37

PROVEAN

Benign

0.58

REVEL

Benign

0.0030

Sift

Benign

0.43

Sift4G

Benign

0.87

Polyphen

0.029

Vest4

0.088

MVP

0.014

MPC

0.22

ClinPred

0.0085

GERP RS

-5.0

Varity_R

0.022

gMVP

0.26

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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