17-36212546-G-C

Variant names:

• chr17-36212546-G-C
• rs372370654
• NM_001291468.2:c.241G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001291468.2(CCL4L2):​c.241G>C​(p.Val81Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V81M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 36)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CCL4L2 NM_001291468.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

Genes affected

CCL4L2 (HGNC:24066): (C-C motif chemokine ligand 4 like 2) This gene is one of several cytokine genes that are clustered on the q-arm of chromosome 17. Cytokines are a family of secreted proteins that function in inflammatory and immunoregulatory processes. The protein encoded by this family member is similar to the chemokine (C-C motif) ligand 4 product, which inhibits HIV entry by binding to the cellular receptor CCR5. The copy number of this gene varies among individuals, where most individuals have one to five copies. This gene copy contains a non-consensus splice acceptor site at the 3' terminal exon found in other highly similar gene copies, and it thus uses other alternative splice sites for the 3' terminal exon, resulting in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085965246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291468.2. 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
	CCL4L2	NM_001291468.2	MANE Select	c.241G>C	p.Val81Leu	missense	Exon 3 of 3	NP_001278397.1
	CCL4L2	NM_001291471.2		c.*113G>C		3_prime_UTR	Exon 3 of 3	NP_001278400.1
	CCL4L2	NM_001291475.2		c.*123G>C		3_prime_UTR	Exon 3 of 3	NP_001278404.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL4L2	ENST00000620576.5	TSL:1 MANE Select	c.241G>C	p.Val81Leu	missense	Exon 3 of 3	ENSP00000479354.1	Q8NHW4-2
	CCL4L2	ENST00000620250.1	TSL:1	c.256G>C	p.Val86Leu	missense	Exon 3 of 3	ENSP00000483609.1	Q8NHW4-1
	CCL4L2	ENST00000620055.4	TSL:1	c.126G>C	p.Thr42Thr	synonymous	Exon 2 of 2	ENSP00000481323.1	Q8NHW4-7

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432752 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 712488

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.0000226 AC: 1 AN: 44262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00 AC: 0 AN: 84482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1090310

Other (OTH) AF: 0.00 AC: 0 AN: 59134

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.14
DANN	Benign	0.95
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.1
Sift4G	Benign	0.088	T
Vest4		0.13
MutPred		0.60		Gain of disorder (P = 0.2084)
MVP		0.014
ClinPred		0.18	T
GERP RS		-2.4

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: rs372370654; hg19: chr17-34539948;