9-34662051-T-C

Position:

• chr9-34662051-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006664.4(CCL27):​c.232A>G​(p.Ile78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,614,194 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.026 (173 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (128 hom.)
• Consequence: CCL27 NM_006664.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.607

Genes affected

CCL27 (HGNC:10626): (C-C motif chemokine ligand 27) This gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The protein encoded by this gene is chemotactic for skin-associated memory T lymphocytes. This cytokine may also play a role in mediating homing of lymphocytes to cutaneous sites. It specifically binds to chemokine receptor 10 (CCR10). Studies of a similar murine protein indicate that these protein-receptor interactions have a pivotal role in T cell-mediated skin inflammation. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026102066).
• BP6: Variant 9-34662051-T-C is Benign according to our data. Variant chr9-34662051-T-C is described in ClinVar as [Benign]. Clinvar id is 768290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL27	NM_006664.4	c.232A>G	p.Ile78Val	missense_variant	3/3	ENST00000259631.5	NP_006655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL27	ENST00000259631.5	c.232A>G	p.Ile78Val	missense_variant	3/3	1	NM_006664.4	ENSP00000259631	P1
CCL27	ENST00000557161.1	n.708A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3959 AN: 152196 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.0216

GnomAD3 exomes AF: 0.00703 AC: 1769 AN: 251486 Hom.: 75 AF XY: 0.00530 AC XY: 721 AN XY: 135916

Gnomad AFR exome AF: 0.0931

Gnomad AMR exome AF: 0.00544

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00255 AC: 3731 AN: 1461880 Hom.: 128 Cov.: 32 AF XY: 0.00219 AC XY: 1590 AN XY: 727244

Gnomad4 AFR exome AF: 0.0864

Gnomad4 AMR exome AF: 0.00588

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.00616

GnomAD4 genome AF: 0.0261 AC: 3982 AN: 152314 Hom.: 173 Cov.: 32 AF XY: 0.0252 AC XY: 1875 AN XY: 74468

Gnomad4 AFR AF: 0.0900

Gnomad4 AMR AF: 0.0110

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.00641 Hom.: 53

Bravo AF: 0.0299

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0887 AC: 391

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00864 AC: 1049

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.3
DANN	Benign	0.75
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	0.41	T
Polyphen		0.033	B
Vest4		0.072
MVP		0.21
MPC		0.067
ClinPred		0.0037	T
GERP RS		0.41
Varity_R		0.034
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs11575594; hg19: chr9-34662048;