17-36104561-C-G

Variant names:

• chr17-36104561-C-G
• rs756740495
• NM_002984.4:c.110C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002984.4(CCL4):​c.110C>G​(p.Ser37Cys) 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 1,460,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCL4 NM_002984.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.231
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002984.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL4	NM_002984.4	MANE Select	c.110C>G	p.Ser37Cys	missense	Exon 2 of 3	NP_002975.1	P13236

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL4	ENST00000615863.2	TSL:1 MANE Select	c.110C>G	p.Ser37Cys	missense	Exon 2 of 3	ENSP00000482259.1	P13236
	CCL4	ENST00000621626.1	TSL:1	c.76+580C>G		intron	N/A	ENSP00000480569.1	Q7M4M2
	CCL4	ENST00000613947.1	TSL:6	n.721C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250502 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460392 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726518

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4734

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.2	T
PhyloP100		0.23
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.65		Gain of sheet (P = 0.0827)
MVP		0.53
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.69
gMVP		0.42

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

Other links and lift over

dbSNP: rs756740495; hg19: chr17-34431954;