Genetic Variant IL21:c.361-23_361-18delGTTACT (chr4-122612945-AAGTAAC-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_021803.4(IL21):c.361-23_361-18delGTTACT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000753 in 1,327,294 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

IL21
NM_021803.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.328

Publications

0 publications found

Variant links:

Genes affected

IL21 (HGNC:6005): (interleukin 21) This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

IL21 Gene-Disease associations (from GenCC):

IL21-related infantile inflammatory bowel disease
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
common variable immunodeficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

IL21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 4-122612945-AAGTAAC-A is Benign according to our data. Variant chr4-122612945-AAGTAAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1637755.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21	NM_021803.4 link	c.361-23_361-18delGTTACT		intron_variant	Intron 3 of 4	ENST00000648588.1	NP_068575.1	Q9HBE4-1A0A224B028
IL21	NM_001207006.3 link	c.361-23_361-18delGTTACT		intron_variant	Intron 3 of 3		NP_001193935.1	Q9HBE4-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL21	ENST00000648588.1 link	c.361-23_361-18delGTTACT	intron_variant	Intron 3 of 4		NM_021803.4	ENSP00000497915.1	Q9HBE4-1
IL21	ENST00000611104.2 link	c.361-23_361-18delGTTACT	intron_variant	Intron 3 of 3	1		ENSP00000477555.1	Q9HBE4-2
IL21	ENST00000647784.1 link	n.213-23_213-18delGTTACT	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.53e-7

AC:

AN:

1327294

Hom.:

AF XY:

0.00000151

AC XY:

AN XY:

663862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29120

American (AMR)

AF:

0.00

AC:

AN:

32254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23198

East Asian (EAS)

AF:

0.00

AC:

AN:

38710

South Asian (SAS)

AF:

0.00

AC:

AN:

76176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4774

European-Non Finnish (NFE)

AF:

9.83e-7

AC:

AN:

1016902

Other (OTH)

AF:

0.00

AC:

AN:

55228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.33

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over