1-168581191-A-T

Position:

• chr1-168581191-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002995.3(XCL1):​c.316A>T​(p.Thr106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,642 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (19 hom.)
• Consequence: XCL1 NM_002995.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035821497).
• BP6: Variant 1-168581191-A-T is Benign according to our data. Variant chr1-168581191-A-T is described in ClinVar as [Benign]. Clinvar id is 780276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00699 (1064/152132) while in subpopulation AFR AF= 0.0242 (1005/41458). AF 95% confidence interval is 0.023. There are 17 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XCL1	NM_002995.3	c.316A>T	p.Thr106Ser	missense_variant	3/3	ENST00000367818.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XCL1	ENST00000367818.4	c.316A>T	p.Thr106Ser	missense_variant	3/3	1	NM_002995.3	P1

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1063 AN: 152014 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00171 AC: 430 AN: 250934 Hom.: 7 AF XY: 0.00129 AC XY: 175 AN XY: 135620

Gnomad AFR exome AF: 0.0220

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000794

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000707 AC: 1033 AN: 1461510 Hom.: 19 Cov.: 30 AF XY: 0.000615 AC XY: 447 AN XY: 727072

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.00152

GnomAD4 genome AF: 0.00699 AC: 1064 AN: 152132 Hom.: 17 Cov.: 32 AF XY: 0.00714 AC XY: 531 AN XY: 74362

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00203 Hom.: 1

Bravo AF: 0.00730

ESP6500AA AF: 0.0195 AC: 86

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00203 AC: 247

Asia WGS AF: 0.00173 AC: 6 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.4
DANN	Benign	0.87
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.035
Sift	Benign	0.040	D
Sift4G	Benign	0.13	T
Polyphen		0.079	B
Vest4		0.065
MutPred		0.11		Gain of sheet (P = 0.0344);
MVP		0.10
MPC		0.10
ClinPred		0.012	T
GERP RS		2.4
Varity_R		0.057
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs113445679; hg19: chr1-168550429;