1-168580184-C-T

Variant names:

• chr1-168580184-C-T
• rs6427130
• NM_002995.3:c.176+7C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000307090 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XCL1	NM_002995.3	c.176+7C>T		splice_region_variant, intron_variant	Intron 2 of 2	ENST00000367818.4	NP_002986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XCL1	ENST00000367818.4	c.176+7C>T		splice_region_variant, intron_variant	Intron 2 of 2	1	NM_002995.3	ENSP00000356792.3
ENSG00000307090	ENST00000823814.1	n.130-3469G>A		intron_variant	Intron 1 of 2

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

GnomAD2 exomes AF: 0.467 AC: 116313 AN: 249168 AF XY: 0.469

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 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

African (AFR) AF: 0.531 AC: 17606 AN: 33184

American (AMR) AF: 0.372 AC: 16527 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 13772 AN: 25994

East Asian (EAS) AF: 0.184 AC: 7285 AN: 39582

South Asian (SAS) AF: 0.396 AC: 33960 AN: 85696

European-Finnish (FIN) AF: 0.526 AC: 27765 AN: 52814

Middle Eastern (MID) AF: 0.558 AC: 3190 AN: 5716

European-Non Finnish (NFE) AF: 0.544 AC: 601044 AN: 1105442

Other (OTH) AF: 0.511 AC: 30621 AN: 59964

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

African (AFR) AF: 0.534 AC: 21966 AN: 41170

American (AMR) AF: 0.455 AC: 6896 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1742 AN: 3450

East Asian (EAS) AF: 0.185 AC: 955 AN: 5154

South Asian (SAS) AF: 0.387 AC: 1844 AN: 4762

European-Finnish (FIN) AF: 0.526 AC: 5440 AN: 10352

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 36724 AN: 67334

Other (OTH) AF: 0.538 AC: 1132 AN: 2106

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
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6427130; hg19: chr1-168549422; COSMIC: COSV107453566; COSMIC: COSV107453566;