chr16-57360546-G-C

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -3 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_StrongBP7

The NM_002990.5(CCL22):c.183G>C (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 0.000000684 (AC=1) in the gnomAD database across 1,461,786 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000116. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCL22 NM_002990.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.0000116 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
	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).
	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>C p.Pro61Pro	synonymous	Exon 2 of 3	Prot: NP_002981.2

CCL22 NM_002990.5

MANE Select

HGVSc / HGVSpc.183G>Cp.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>C p.Pro61Pro	synonymous	Exon 2 of 3	Prot: ENSP00000219235.4 UniProt:
	CCL22 ENST00000941195.1		c.183G>C p.Pro61Pro	synonymous	Exon 3 of 4	Prot: ENSP00000611254.1 UniProt:

CCL22 ENST00000219235.5

TSL:1MANE Select

HGVSc / HGVSpc.183G>Cp.Pro61Pro

Exon rankExon 2 of 3

synonymous

Prot: ENSP00000219235.4UniProt: O00626

CCL22 ENST00000941195.1

HGVSc / HGVSpc.183G>Cp.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 4 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD2 exomes	AF: 0.00000398	AC:1	Hom:	AN:251370	Cov:
GnomAD4 exome	AF: 6.84e-7	AC:1	Hom:0	AN:1461786	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 4 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	12
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.9
DANN	Benign	0.50
GPN-Star LLR	N/A	-2.4
GPN-Star score	N/A	2.4
PhyloP100	Benign	0.69

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.020
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