rs6427130

Positions:

• chr1-168580184-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002995.3(XCL1):​c.176+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,603,556 control chromosomes in the GnomAD database, including 207,970 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (19828 hom., cov: 32)
  • Exomes 𝑓: 0.52 (188142 hom.)
• Consequence: XCL1 NM_002995.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001527
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

Genes affected

XCL1 (HGNC:10645): (X-C motif chemokine ligand 1) This antimicrobial gene encodes a member of the chemokine superfamily. Chemokines function in inflammatory and immunological responses, inducing leukocyte migration and activation. The encoded protein is a member of the C-chemokine subfamily, retaining only two of four cysteines conserved in other chemokines, and is thought to be specifically chemotactic for T cells. This gene and a closely related family member are located on the long arm of chromosome 1. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XCL1	NM_002995.3	c.176+7C>T		splice_region_variant, intron_variant		ENST00000367818.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XCL1	ENST00000367818.4	c.176+7C>T		splice_region_variant, intron_variant		1	NM_002995.3	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77272 AN: 150566 Hom.: 19795 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.539

GnomAD3 exomes AF: 0.467 AC: 116313 AN: 249168 Hom.: 27323 AF XY: 0.469 AC XY: 63143 AN XY: 134644

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.390

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.541

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.517 AC: 751770 AN: 1452868 Hom.: 188142 Cov.: 42 AF XY: 0.514 AC XY: 371526 AN XY: 722716

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.513 AC: 77343 AN: 150688 Hom.: 19828 Cov.: 32 AF XY: 0.509 AC XY: 37444 AN XY: 73592

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.538

Alfa AF: 0.535 Hom.: 9454

Bravo AF: 0.514

Asia WGS AF: 0.333 AC: 1160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6427130; hg19: chr1-168549422;