rs141454356

Variant names:

• chr16-57360546-G-A
• rs141454356
• NM_002990.5:c.183G>A
• CCL22 p.Pro61Pro

Your query was ambiguous. Multiple possible variants found:

• chr16-57360546-G-A
• chr16-57360546-G-C

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

-7 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -7 classification points (ACMG Germline Pathogenicity v2019). BP4_StrongBP6_ModerateBP7

The NM_002990.5(CCL22):c.183G>A (p.Pro61Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00103 (AC=1,666) in the gnomAD database across 1,614,030 control chromosomes, including 1 homozygote. The grpmax filtering allele frequency (95% CI) is 0.00131. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: CCL22 NM_002990.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.693
• Publications: 0 publications found

Genes affected

CCL22 (HGNC:10621): (C-C motif chemokine ligand 22) This antimicrobial gene is one of several Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 16. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for monocytes, dendritic cells, natural killer cells and for chronically activated T lymphocytes. It also displays a mild activity for primary activated T lymphocytes and has no chemoattractant activity for neutrophils, eosinophils and resting T lymphocytes. The product of this gene binds to chemokine receptor CCR4. This chemokine may play a role in the trafficking of activated T lymphocytes to inflammatory sites and other aspects of activated T lymphocyte physiology. [provided by RefSeq, Sep 2014]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -7 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002990.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CCL22 NM_002990.5	MANE Select	c.183G>A p.Pro61Pro	synonymous	Exon 2 of 3	Prot: NP_002981.2

CCL22 NM_002990.5

MANE Select

HGVSc / HGVSpc.183G>Ap.Pro61Pro

Exon rankExon 2 of 3

synonymous

Prot: NP_002981.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CCL22 ENST00000219235.5	TSL:1MANE Select	c.183G>A p.Pro61Pro	synonymous	Exon 2 of 3	Prot: ENSP00000219235.4 UniProt:
	CCL22 ENST00000941195.1		c.183G>A p.Pro61Pro	synonymous	Exon 3 of 4	Prot: ENSP00000611254.1 UniProt:

CCL22 ENST00000219235.5

TSL:1MANE Select

HGVSc / HGVSpc.183G>Ap.Pro61Pro

Exon rankExon 2 of 3

synonymous

Prot: ENSP00000219235.4UniProt: O00626

CCL22 ENST00000941195.1

HGVSc / HGVSpc.183G>Ap.Pro61Pro

Exon rankExon 3 of 4

synonymous

Prot: ENSP00000611254.1UniProt: O00626

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.000565	AC:86	Hom:0	AN:152244	Cov:33
GnomAD2 exomes	AF: 0.000493	AC:124	Hom:	AN:251370	Cov:
GnomAD4 exome	AF: 0.00108	AC:1580	Hom:1	AN:1461786	Cov:32
GnomAD4 genome	AF: 0.000565	AC:86	Hom:0	AN:152244	Cov:33
TOPMed (Bravo)	AF: 0.000654	AC:173	Hom:0	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.000720	AC:48	Hom:0	AN:66686	Cov:
Local & regional cohorts 5 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.000427	AC:1	Hom:0	AN:2342	Cov:
ESP6500 (Exome Variant Server)	AF: 0.000616	AC:8	Hom:	AN:12996	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.00000800	AC:1	Hom:0	AN:122324	Cov:
Turkish Variome	AF: 0.000354	AC:2	Hom:0	AN:5168	Cov:
UK10K	AF: 0.00185	AC:14	Hom:	AN:7562	Cov:

Showing 11 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.00234 *	26	11112	0.00193 *	34	17614
BipEx(Bipolar disorder (including schizoaffective))	0.00148	42	28420	0.00107	31	28844
Epi25(Epilepsy)	0.000906	38	41958	0.000897	60	66884
SCHEMA(Schizophrenia)	0.000474	41	86428	0.000603	84	139370

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	12
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.61
GPN-Star LLR	N/A	-1.1
GPN-Star score	N/A	1.1
Mutation Taster	N/A	100/0	polymorphism
PhyloP100	Benign	0.69

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.040	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs141454356;

hg19: chr16-57394458;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar