chr16-57360481-T-C

Variant names:

• chr16-57360481-T-C
• rs41398344
• NM_002990.5:c.118T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002990.5(CCL22):​c.118T>C​(p.Tyr40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,614,214 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0078 (57 hom.)
• Consequence: CCL22 NM_002990.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.21
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005359113).
• BP6: Variant 16-57360481-T-C is Benign according to our data. Variant chr16-57360481-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 769900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002990.5. 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
	CCL22	NM_002990.5	MANE Select	c.118T>C	p.Tyr40His	missense	Exon 2 of 3	NP_002981.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL22	ENST00000219235.5	TSL:1 MANE Select	c.118T>C	p.Tyr40His	missense	Exon 2 of 3	ENSP00000219235.4
	CCL22	ENST00000941195.1		c.118T>C	p.Tyr40His	missense	Exon 3 of 4	ENSP00000611254.1

Frequencies

GnomAD3 genomes AF: 0.00470 AC: 715 AN: 152234 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00521 AC: 1311 AN: 251462 AF XY: 0.00527

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00840

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00777 AC: 11353 AN: 1461862 Hom.: 57 Cov.: 32 AF XY: 0.00771 AC XY: 5610 AN XY: 727232

African (AFR) AF: 0.000986 AC: 33 AN: 33480

American (AMR) AF: 0.00277 AC: 124 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00210 AC: 55 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00519 AC: 448 AN: 86258

European-Finnish (FIN) AF: 0.00148 AC: 79 AN: 53414

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.00916 AC: 10181 AN: 1111986

Other (OTH) AF: 0.00697 AC: 421 AN: 60396

GnomAD4 genome AF: 0.00469 AC: 715 AN: 152352 Hom.: 4 Cov.: 33 AF XY: 0.00448 AC XY: 334 AN XY: 74496

African (AFR) AF: 0.00144 AC: 60 AN: 41582

American (AMR) AF: 0.00503 AC: 77 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00496 AC: 24 AN: 4834

European-Finnish (FIN) AF: 0.000564 AC: 6 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00773 AC: 526 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00649 Hom.: 14

Bravo AF: 0.00474

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00884 AC: 76

ExAC AF: 0.00549 AC: 667

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00900

EpiControl AF: 0.00753

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.2
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.039
Sift	Uncertain	0.029	D
Sift4G	Benign	0.10	T
Polyphen		0.062	B
Vest4		0.40
MVP		0.088
MPC		0.76
ClinPred		0.015	T
GERP RS		3.1
Varity_R		0.23
gMVP		0.86
Mutation Taster		=99/1	polymorphism

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

dbSNP: rs41398344; hg19: chr16-57394393;