chr17-36104569-G-T

Variant names:

• chr17-36104569-G-T
• rs200881527
• NM_002984.4:c.118G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002984.4(CCL4):​c.118G>T​(p.Ala40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000664 in 1,460,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: CCL4 NM_002984.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08015865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL4	NM_002984.4	c.118G>T	p.Ala40Ser	missense_variant	Exon 2 of 3	ENST00000615863.2	NP_002975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL4	ENST00000615863.2	c.118G>T	p.Ala40Ser	missense_variant	Exon 2 of 3	1	NM_002984.4	ENSP00000482259.1
CCL4	ENST00000621626.1	c.76+588G>T		intron_variant	Intron 1 of 1	1		ENSP00000480569.1
CCL4	ENST00000613947.1	n.729G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 250492 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135466

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 97 AN: 1460550 Hom.: 0 Cov.: 33 AF XY: 0.0000771 AC XY: 56 AN XY: 726582

Gnomad4 AFR exome AF: 0.0000598

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: 0.0000845

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.010
DANN	Benign	0.21
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.046	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.24		Gain of disorder (P = 0.0553);
MVP		0.15
ClinPred		0.056	T
GERP RS		-0.86
Varity_R		0.10
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200881527; hg19: chr17-34431962;