NM_002996.6:c.191+957A>G

Variant names:

• chr16-57380711-A-G
• rs170361
• NM_002996.6:c.191+957A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002996.6(CX3CL1):​c.191+957A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,022 control chromosomes in the GnomAD database, including 46,383 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 0.78 (46383 hom., cov: 30)
• Consequence: CX3CL1 NM_002996.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 12 publications found

Genes affected

CX3CL1 (HGNC:10647): (C-X3-C motif chemokine ligand 1) This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002996.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	NM_002996.6	MANE Select	c.191+957A>G		intron	N/A	NP_002987.1
	CX3CL1	NM_001304392.3		c.-64-1319A>G		intron	N/A	NP_001291321.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	ENST00000006053.7	TSL:1 MANE Select	c.191+957A>G		intron	N/A	ENSP00000006053.6
	CX3CL1	ENST00000565912.1	TSL:1	c.77+957A>G		intron	N/A	ENSP00000464114.1
	CX3CL1	ENST00000563383.1	TSL:5	c.209+957A>G		intron	N/A	ENSP00000456830.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118401 AN: 151904 Hom.: 46353 Cov.: 30

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.779 AC: 118490 AN: 152022 Hom.: 46383 Cov.: 30 AF XY: 0.780 AC XY: 57945 AN XY: 74310

African (AFR) AF: 0.729 AC: 30190 AN: 41430

American (AMR) AF: 0.740 AC: 11311 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2789 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3771 AN: 5158

South Asian (SAS) AF: 0.715 AC: 3448 AN: 4824

European-Finnish (FIN) AF: 0.873 AC: 9221 AN: 10566

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55141 AN: 67982

Other (OTH) AF: 0.791 AC: 1667 AN: 2108

Alfa AF: 0.792 Hom.: 120858

Bravo AF: 0.765

Asia WGS AF: 0.750 AC: 2609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.51
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs170361; hg19: chr16-57414623;