17-36104568-C-T

Position:

• chr17-36104568-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_002984.4(CCL4):​c.117C>T​(p.Thr39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,612,602 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0079 (14 hom., cov: 31)
  • Exomes 𝑓: 0.00087 (18 hom.)
• Consequence: CCL4 NM_002984.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769

Genes affected

CCL4 (HGNC:10630): (C-C motif chemokine ligand 4) The protein encoded by this gene is a mitogen-inducible monokine and is one of the major HIV-suppressive factors produced by CD8+ T-cells. The encoded protein is secreted and has chemokinetic and inflammatory functions. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.769 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00789 (1201/152130) while in subpopulation AFR AF= 0.0274 (1138/41496). AF 95% confidence interval is 0.0261. There are 14 homozygotes in gnomad4. There are 568 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL4	NM_002984.4	c.117C>T	p.Thr39=	synonymous_variant	2/3	ENST00000615863.2	NP_002975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL4	ENST00000615863.2	c.117C>T	p.Thr39=	synonymous_variant	2/3	1	NM_002984.4	ENSP00000482259	P1
CCL4	ENST00000621626.1	c.76+587C>T		intron_variant		1		ENSP00000480569
CCL4	ENST00000613947.1	n.728C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00785 AC: 1194 AN: 152012 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00336

GnomAD4 exome AF: 0.000871 AC: 1272 AN: 1460472 Hom.: 18 Cov.: 33 AF XY: 0.000772 AC XY: 561 AN XY: 726546

Gnomad4 AFR exome AF: 0.0289

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000414

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00789 AC: 1201 AN: 152130 Hom.: 14 Cov.: 31 AF XY: 0.00764 AC XY: 568 AN XY: 74362

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.0103 Hom.: 2

Bravo AF: 0.00925

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1719146; hg19: chr17-34431961;