Variant chr1-168542093-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003175.4(XCL2):c.76G>A(p.Val26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,524,990 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V26V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00033 ( 39 hom. )

Consequence

XCL2
NM_003175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.190

Variant links:

Genes affected

XCL2 (HGNC:10646): (X-C motif chemokine ligand 2) Predicted to enable CCR chemokine receptor binding activity and chemokine activity. Predicted to be involved in several processes, including cellular response to cytokine stimulus; leukocyte chemotaxis; and positive regulation of T cell chemotaxis. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

XCL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006197512).

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XCL2	NM_003175.4 linkuse as main transcript	c.76G>A	p.Val26Ile	missense_variant	2/3	ENST00000367819.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XCL2	ENST00000367819.3 linkuse as main transcript	c.76G>A	p.Val26Ile	missense_variant	2/3	1	NM_003175.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000272

AC:

AN:

146814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000700

Gnomad ASJ

AF:

0.00615

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000210

Gnomad OTH

AF:

0.000999

GnomAD3 exomes

AF:

0.000640

AC:

139

AN:

217224

Hom.:

AF XY:

0.000653

AC XY:

AN XY:

117950

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000159

Gnomad ASJ exome

AF:

0.00985

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000789

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000333

AC:

459

AN:

1378064

Hom.:

Cov.:

AF XY:

0.000372

AC XY:

255

AN XY:

684634

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00863

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000783

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.000808

GnomAD4 genome

AF:

0.000272

AC:

AN:

146926

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

71326

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.0000699

Gnomad4 ASJ

AF:

0.00615

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000210

Gnomad4 OTH

AF:

0.000988

Alfa

AF:

0.000874

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000468

AC:

ExAC

AF:

0.000533

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.76G>A (p.V26I) alteration is located in exon 2 (coding exon 2) of the XCL2 gene. This alteration results from a G to A substitution at nucleotide position 76, causing the valine (V) at amino acid position 26 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0081

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.45

M_CAP

Benign

0.0019

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.37

REVEL

Benign

0.043

Sift

Benign

0.034

Sift4G

Benign

0.24

Polyphen

0.32

Vest4

0.12

MVP

0.15

MPC

0.21

ClinPred

0.022

GERP RS

2.5

Varity_R

0.044

gMVP

0.088

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over