17-35977636-G-C

Variant names:

• chr17-35977636-G-C
• rs1258056740
• NM_004590.4:c.293C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004590.4(CCL16):​c.293C>G​(p.Thr98Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCL16 NM_004590.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.850

Genes affected

CCL16 (HGNC:10614): (C-C motif chemokine ligand 16) This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. 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 lymphocytes and monocytes but not for neutrophils. This cytokine also shows a potent myelosuppressive activity and suppresses proliferation of myeloid progenitor cells. The expression of this gene is upregulated by IL-10. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04576564).
• BP6: Variant 17-35977636-G-C is Benign according to our data. Variant chr17-35977636-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3139715.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL16	NM_004590.4	c.293C>G	p.Thr98Ser	missense_variant	Exon 3 of 3	ENST00000611905.2	NP_004581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL16	ENST00000611905.2	c.293C>G	p.Thr98Ser	missense_variant	Exon 3 of 3	1	NM_004590.4	ENSP00000478024.1
CCL16	ENST00000610493.1	n.*363C>G		non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000478934.1
CCL16	ENST00000613642.4	n.215C>G		non_coding_transcript_exon_variant	Exon 2 of 3	3		ENSP00000478592.1
CCL16	ENST00000610493.1	n.*363C>G		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000478934.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460216 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 27, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.0
DANN	Benign	0.65
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.28	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.042
MutPred		0.22		Gain of disorder (P = 0.0801);
MVP		0.25
ClinPred		0.056	T
GERP RS		1.8
Varity_R		0.18
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: rs1258056740; hg19: chr17-34304672;