rs6427130

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-168580184-C-G
• chr1-168580184-C-T

Variant summary

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

The NM_002995.3(XCL1):​c.176+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XCL1 NM_002995.3 splice_region, intron
• Scores: Splicing: ADA: 0.00007057
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 0 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: 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=-0.86).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150666 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453542 Hom.: 0 Cov.: 42 AF XY: 0.00000138 AC XY: 1 AN XY: 723100

African (AFR) AF: 0.00 AC: 0 AN: 33218

American (AMR) AF: 0.00 AC: 0 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 85792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105864

Other (OTH) AF: 0.00 AC: 0 AN: 59988

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150666 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73524

African (AFR) AF: 0.00 AC: 0 AN: 41068

American (AMR) AF: 0.00 AC: 0 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67378

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.39
DANN	Benign	0.59
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000071
dbscSNV1_RF	Benign	0.0
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: rs6427130; hg19: chr1-168549422;