chr3-136989562-C-G

Position:

• chr3-136989562-C-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_144717.4(IL20RB):​c.528C>G​(p.Ala176Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,613,696 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (5 hom.)
• Consequence: IL20RB NM_144717.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0510

Genes affected

IL20RB (HGNC:6004): (interleukin 20 receptor subunit beta) IL20RB and IL20RA (MIM 605620) form a heterodimeric receptor for interleukin-20 (IL20; MIM 605619) (Blumberg et al., 2001 [PubMed 11163236]).[supplied by OMIM, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-136989562-C-G is Benign according to our data. Variant chr3-136989562-C-G is described in ClinVar as [Benign]. Clinvar id is 774849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.051 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL20RB	NM_144717.4	c.528C>G	p.Ala176Ala	synonymous_variant	4/7	ENST00000329582.9	NP_653318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL20RB	ENST00000329582.9	c.528C>G	p.Ala176Ala	synonymous_variant	4/7	1	NM_144717.4	ENSP00000328133.4

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 242 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00165 AC: 413 AN: 251002 Hom.: 3 AF XY: 0.00192 AC XY: 261 AN XY: 135684

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00137

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00259

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00217 AC: 3171 AN: 1461448 Hom.: 5 Cov.: 31 AF XY: 0.00218 AC XY: 1587 AN XY: 727024

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00244

Gnomad4 OTH exome AF: 0.00346

GnomAD4 genome AF: 0.00159 AC: 242 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74442

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00141 Hom.: 1

Bravo AF: 0.00169

EpiCase AF: 0.00414

EpiControl AF: 0.00356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.95
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs244405; hg19: chr3-136708404;