chr22-49998181-C-T

Position:

chr22-49998181-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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:

IL17REL (HGNC:):

IL17REL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -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 id is 2272813.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17REL	NM_001371417.1 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	10/15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	10/15		NP_001358345.1
IL17REL	NM_001001694.3 linkuse as main transcript	c.730G>A	p.Gly244Ser	missense_variant	10/15		NP_001001694.2	Q6ZVW7
IL17REL	XR_001755245.2 linkuse as main transcript	n.1065G>A		non_coding_transcript_exon_variant	10/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17REL	ENST00000695950.1 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	10/15		NM_001371417.1	ENSP00000512282.1	A0A8Q3WKV1
IL17REL	ENST00000695951.1 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	10/15			ENSP00000512283.1	A0A8Q3WLX3
IL17REL	ENST00000389983.7 linkuse as main transcript	n.*865G>A		non_coding_transcript_exon_variant	10/15	2		ENSP00000374633.3	Q6ZVW7
IL17REL	ENST00000389983.7 linkuse as main transcript	n.*865G>A		3_prime_UTR_variant	10/15	2		ENSP00000374633.3	Q6ZVW7

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

GnomAD3 exomes

AF:

0.0000419

AC:

AN:

238590

Hom.:

AF XY:

0.0000383

AC XY:

AN XY:

130504

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 SAS exome

AF:

0.0000331

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

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000193

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000100

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.066

DANN

Benign

0.52

DEOGEN2

Benign

0.00050

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.32

T;.

M_CAP

Benign

0.0013

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.58

N;N

REVEL

Benign

0.0030

Sift

Benign

0.43

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.029

B;B

Vest4

0.088

MVP

0.014

MPC

0.22

ClinPred

0.0085

GERP RS

-5.0

Varity_R

0.022

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over