rs41507946

Variant names:

• chr17-34255522-C-A
• rs41507946
• NM_002982.4:c.76+97C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-34255522-C-A
• chr17-34255522-C-G
• chr17-34255522-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002982.4(CCL2):​c.76+97C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000109 in 916,602 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 0 publications found

Genes affected

CCL2 (HGNC:10618): (C-C motif chemokine ligand 2) This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are 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 and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]

CCL2 Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL2	NM_002982.4	c.76+97C>A		intron_variant	Intron 1 of 2	ENST00000225831.4	NP_002973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL2	ENST00000225831.4	c.76+97C>A		intron_variant	Intron 1 of 2	1	NM_002982.4	ENSP00000225831.4
CCL2	ENST00000624362.2	n.238C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
CCL2	ENST00000580907.6	c.76+97C>A		intron_variant	Intron 1 of 1	2		ENSP00000462156.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000109 AC: 1 AN: 916602 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 471074

⚠️ 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: 21800

American (AMR) AF: 0.00 AC: 0 AN: 34380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19678

East Asian (EAS) AF: 0.00 AC: 0 AN: 34916

South Asian (SAS) AF: 0.00 AC: 0 AN: 67602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4546

European-Non Finnish (NFE) AF: 0.00000155 AC: 1 AN: 646636

Other (OTH) AF: 0.00 AC: 0 AN: 41828

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.7
DANN	Benign	0.82
PhyloP100		-0.18
PromoterAI		-0.025	Neutral

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: rs41507946; hg19: chr17-32582541;