4-122620683-A-T

Variant names:

• chr4-122620683-A-T
• NM_021803.4:c.204+18T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_021803.4(IL21):​c.204+18T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,453,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: IL21 NM_021803.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

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-AS1 (HGNC:40299): (IL21 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 4-122620683-A-T is Benign according to our data. Variant chr4-122620683-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1638346.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	c.204+18T>A		intron_variant	Intron 2 of 4	ENST00000648588.1	NP_068575.1
IL21	NM_001207006.3	c.204+18T>A		intron_variant	Intron 2 of 3		NP_001193935.1
IL21-AS1	NR_104126.1	n.709-185A>T		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21	ENST00000648588.1	c.204+18T>A		intron_variant	Intron 2 of 4		NM_021803.4	ENSP00000497915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1453230 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 722922

African (AFR) AF: 0.0000304 AC: 1 AN: 32942

American (AMR) AF: 0.00 AC: 0 AN: 43442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25830

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 84680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.00000722 AC: 8 AN: 1108462

Other (OTH) AF: 0.00 AC: 0 AN: 59978

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 21, 2022

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
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		1.5
PromoterAI		-0.0033	Neutral

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

Other links and lift over

hg19: chr4-123541838;