17-34319542-C-T

Position:

• chr17-34319542-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005623.3(CCL8):​c.41C>T​(p.Ala14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,613,840 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 0.0069 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (10 hom.)
• Consequence: CCL8 NM_005623.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.346

Genes affected

CCL8 (HGNC:10635): (C-C motif chemokine ligand 8) This antimicrobial gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes, lymphocytes, basophils and eosinophils. By recruiting leukocytes to sites of inflammation this cytokine may contribute to tumor-associated leukocyte infiltration and to the antiviral state against HIV infection. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065965056).
• BP6: Variant 17-34319542-C-T is Benign according to our data. Variant chr17-34319542-C-T is described in ClinVar as [Benign]. Clinvar id is 714732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00694 (1057/152332) while in subpopulation AFR AF= 0.024 (998/41572). AF 95% confidence interval is 0.0228. There are 12 homozygotes in gnomad4. There are 499 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL8	NM_005623.3	c.41C>T	p.Ala14Val	missense_variant	1/3	ENST00000394620.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL8	ENST00000394620.2	c.41C>T	p.Ala14Val	missense_variant	1/3	1	NM_005623.3	P1

Frequencies

GnomAD3 genomes AF: 0.00690 AC: 1050 AN: 152214 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00168 AC: 421 AN: 250616 Hom.: 5 AF XY: 0.00123 AC XY: 167 AN XY: 135406

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000531

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000672 AC: 982 AN: 1461508 Hom.: 10 Cov.: 30 AF XY: 0.000583 AC XY: 424 AN XY: 727072

Gnomad4 AFR exome AF: 0.0244

Gnomad4 AMR exome AF: 0.000962

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00694 AC: 1057 AN: 152332 Hom.: 12 Cov.: 32 AF XY: 0.00670 AC XY: 499 AN XY: 74496

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00138 Hom.: 6

Bravo AF: 0.00813

ESP6500AA AF: 0.0204 AC: 90

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00219 AC: 266

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.92
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
REVEL	Benign	0.014
Sift4G	Benign	0.30	T
Polyphen		0.16	B
Vest4		0.13
MVP		0.42
MPC		0.12
ClinPred		0.0027	T
GERP RS		-1.4
Varity_R		0.043
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs35401229; hg19: chr17-32646561; COSMIC: COSV99061255;