Genetic Variant NM_018725.4:c.946+1206A>C (chr3-53861434-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018725.4(IL17RB):c.946+1206A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,024 control chromosomes in the GnomAD database, including 10,122 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 0.36 ( 10122 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

IL17RB
NM_018725.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.497

Publications

6 publications found

Variant links:

Genes affected

IL17RB (HGNC:18015): (interleukin 17 receptor B) The protein encoded by this gene is a cytokine receptor. This receptor specifically binds to IL17B and IL17E, but does not bind to IL17 and IL17C. This receptor has been shown to mediate the activation of NF-kappaB and the production of IL8 induced by IL17E. The expression of the rat counterpart of this gene was found to be significantly up-regulated during intestinal inflammation, which suggested the immunoregulatory activity of this receptor. [provided by RefSeq, Jul 2008]

IL17RB links:

ENSG00000271976 (HGNC:):

ENSG00000271976 links:

ACTR8 (HGNC:14672): (actin related protein 8) Predicted to enable ATP binding activity. Predicted to be involved in chromatin remodeling; double-strand break repair; and regulation of transcription, DNA-templated. Located in centrosome and nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACTR8 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RB	NM_018725.4 link	c.946+1206A>C		intron_variant	Intron 10 of 10	ENST00000288167.8	NP_061195.2	Q9NRM6-1
ACTR8	XM_005265587.6 link	c.*3631T>G		3_prime_UTR_variant	Exon 14 of 14		XP_005265644.1	Q9H981-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL17RB	ENST00000288167.8 link	c.946+1206A>C	intron_variant	Intron 10 of 10	1	NM_018725.4	ENSP00000288167.3	Q9NRM6-1
ENSG00000271976	ENST00000607783.1 link	n.143T>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
IL17RB	ENST00000494338.1 link	c.898+1206A>C	intron_variant	Intron 9 of 9	5		ENSP00000418638.1	C9IZN0
IL17RB	ENST00000475124.1 link	n.1979+1206A>C	intron_variant	Intron 9 of 9	2

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54675

AN:

151906

Hom.:

10117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.403

Gnomad AMI

AF:

0.452

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.332

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.360

AC:

54711

AN:

152024

Hom.:

10122

Cov.:

AF XY:

0.360

AC XY:

26753

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.403

AC:

16679

AN:

41436

American (AMR)

AF:

0.330

AC:

5041

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1081

AN:

3468

East Asian (EAS)

AF:

0.483

AC:

2493

AN:

5164

South Asian (SAS)

AF:

0.350

AC:

1689

AN:

4824

European-Finnish (FIN)

AF:

0.313

AC:

3298

AN:

10552

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23241

AN:

67976

Other (OTH)

AF:

0.328

AC:

692

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1748

3496

5244

6992

8740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.348

Hom.:

1142

Bravo

AF:

0.361

Asia WGS

AF:

0.398

AC:

1390

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.4

(source)

DANN

Benign

0.39

PhyloP100

0.50

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