chr22-49996768-C-A

Variant names:

• chr22-49996768-C-A
• rs541077021
• NM_001371417.1:c.1431G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001371417.1(IL17REL):​c.1431G>T​(p.Pro477Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL17REL NM_001371417.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.93
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-49996768-C-A is Benign according to our data. Variant chr22-49996768-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2653357.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17REL	NM_001371417.1	MANE Select	c.1431G>T	p.Pro477Pro	synonymous	Exon 15 of 15	NP_001358346.1	Q6ZVW7-1
	IL17REL	NM_001371416.1		c.*137G>T		3_prime_UTR	Exon 15 of 15	NP_001358345.1	A0A8Q3WLX3
	IL17REL	NM_001001694.3		c.*137G>T		3_prime_UTR	Exon 15 of 15	NP_001001694.2	Q6ZVW7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17REL	ENST00000695950.1	MANE Select	c.1431G>T	p.Pro477Pro	synonymous	Exon 15 of 15	ENSP00000512282.1	Q6ZVW7-1
	IL17REL	ENST00000695951.1		c.*137G>T		3_prime_UTR	Exon 15 of 15	ENSP00000512283.1	A0A8Q3WLX3
	IL17REL	ENST00000389983.7	TSL:2	n.*1283G>T		non_coding_transcript_exon	Exon 15 of 15	ENSP00000374633.3	A0AAA9X3B1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 331700 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 171762

African (AFR) AF: 0.00 AC: 0 AN: 7988

American (AMR) AF: 0.00 AC: 0 AN: 10110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10804

East Asian (EAS) AF: 0.00 AC: 0 AN: 22746

South Asian (SAS) AF: 0.00 AC: 0 AN: 27120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 206320

Other (OTH) AF: 0.00 AC: 0 AN: 20366

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.51
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs541077021; hg19: chr22-50435197;