Genetic Variant NM_014339.7:c.1046-312T>A (chr22-17107415-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014339.7(IL17RA):c.1046-312T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,184 control chromosomes in the GnomAD database, including 4,693 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 0.21 ( 4693 hom., cov: 33)

Consequence

IL17RA
NM_014339.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

13 publications found

Variant links:

Genes affected

IL17RA (HGNC:5985): (interleukin 17 receptor A) Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]

IL17RA Gene-Disease associations (from GenCC):

immunodeficiency 51
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
chronic mucocutaneous candidiasis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IL17RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.1046-312T>A		intron_variant	Intron 11 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2 link	c.944-312T>A		intron_variant	Intron 10 of 11		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11 link	c.1046-312T>A		intron_variant	Intron 11 of 12	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2 link	c.944-312T>A		intron_variant	Intron 10 of 11	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32220

AN:

152066

Hom.:

4680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.0291

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.212

AC:

32273

AN:

152184

Hom.:

4693

Cov.:

AF XY:

0.209

AC XY:

15558

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.405

AC:

16809

AN:

41476

American (AMR)

AF:

0.231

AC:

3533

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

788

AN:

3472

East Asian (EAS)

AF:

0.0288

AC:

149

AN:

5182

South Asian (SAS)

AF:

0.127

AC:

611

AN:

4818

European-Finnish (FIN)

AF:

0.127

AC:

1350

AN:

10606

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8378

AN:

68008

Other (OTH)

AF:

0.226

AC:

476

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1199

2398

3598

4797

5996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.0806

Hom.:

120

Bravo

AF:

0.229

Asia WGS

AF:

0.0950

AC:

332

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.18

(source)

DANN

Benign

0.60

PhyloP100

-1.0

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over