NM_002996.6:c.191+9T>C

Variant names:

• chr16-57379763-T-C
• rs117270130
• NM_002996.6:c.191+9T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002996.6(CX3CL1):​c.191+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,614,158 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (19 hom.)
• Consequence: CX3CL1 NM_002996.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.694
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-57379763-T-C is Benign according to our data. Variant chr16-57379763-T-C is described in ClinVar as Benign. ClinVar VariationId is 774923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 19 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	NM_002996.6	MANE Select	c.191+9T>C		intron	N/A	NP_002987.1	P78423
	CX3CL1	NM_001304392.3		c.-64-2267T>C		intron	N/A	NP_001291321.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	ENST00000006053.7	TSL:1 MANE Select	c.191+9T>C		intron	N/A	ENSP00000006053.6	P78423
	CX3CL1	ENST00000565912.1	TSL:1	c.77+9T>C		intron	N/A	ENSP00000464114.1	J3QRA1
	CX3CL1	ENST00000563383.1	TSL:5	c.209+9T>C		intron	N/A	ENSP00000456830.1	H3BSR6

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 487 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00567

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00332 AC: 834 AN: 251088 AF XY: 0.00327

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.000895

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00337

Gnomad NFE exome AF: 0.00562

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00468 AC: 6845 AN: 1461782 Hom.: 19 Cov.: 31 AF XY: 0.00451 AC XY: 3281 AN XY: 727178

African (AFR) AF: 0.000418 AC: 14 AN: 33474

American (AMR) AF: 0.00228 AC: 102 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000880 AC: 23 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000649 AC: 56 AN: 86256

European-Finnish (FIN) AF: 0.00301 AC: 161 AN: 53414

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.00561 AC: 6235 AN: 1111922

Other (OTH) AF: 0.00401 AC: 242 AN: 60394

GnomAD4 genome AF: 0.00320 AC: 488 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.00305 AC XY: 227 AN XY: 74520

African (AFR) AF: 0.000866 AC: 36 AN: 41586

American (AMR) AF: 0.00183 AC: 28 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00567 AC: 386 AN: 68036

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00400 Hom.: 1

Bravo AF: 0.00306

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.47
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism

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: rs117270130; hg19: chr16-57413675;