rs2234355

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006564.2(CXCR6):c.7G>A(p.Glu3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 1,612,094 control chromosomes in the GnomAD database, including 7,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 4086 hom., cov: 32)

Exomes 𝑓: 0.014 ( 3628 hom. )

Consequence

CXCR6
NM_006564.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

Publications

20 publications found

Variant links:

Genes affected

CXCR6 (HGNC:16647): (C-X-C motif chemokine receptor 6) The protein encoded by this gene is a G protein-coupled receptor with seven transmembrane domains that belongs to the CXC chemokine receptor family. This family also includes CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, and CXCR7. This gene, which maps to the chemokine receptor gene cluster, is expressed in several T lymphocyte subsets and bone marrow stromal cells. The encoded protein and its exclusive ligand, chemokine ligand 16 (CCL16), are part of a signalling pathway that regulates T lymphocyte migration to various peripheral tissues (the liver, spleen red pulp, intestine, lungs, and skin) and promotes cell-cell interaction with dendritic cells and fibroblastic reticular cells. CXCR6/CCL16 also controls the localization of resident memory T lymphocytes to different compartments of the lung and maintains airway resident memory T lymphocytes, which are an important first line of defense against respiratory pathogens. The encoded protein serves as an entry coreceptor used by HIV-1 and SIV to enter target cells, in conjunction with CD4. [provided by RefSeq, Aug 2020]

CXCR6 links:

FYCO1 (HGNC:14673): (FYVE and coiled-coil domain autophagy adaptor 1) The gene encodes a Rab7 adapter protein that is implicated in the microtubule transport of autophagosomes. The encoded protein contains a RUN domain, a FYVE-type zinc finger domain, and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P), the autophagosome marker LC3, and the kinesin KIF5. Mutations in this gene are associated with inclusion body myositis (IBM) and autosomal recessive congenital cataracts (CATC2). [provided by RefSeq, Aug 2020]

FYCO1 Gene-Disease associations (from GenCC):

cataract 18
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FYCO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.6104193E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR6	NM_006564.2 link	c.7G>A	p.Glu3Lys	missense_variant	Exon 2 of 2	ENST00000304552.5	NP_006555.1
FYCO1	NM_024513.4 link	c.3944+8761C>T		intron_variant	Intron 14 of 17	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR6	ENST00000304552.5 link	c.7G>A	p.Glu3Lys	missense_variant	Exon 2 of 2	1	NM_006564.2	ENSP00000304414.4
FYCO1	ENST00000296137.7 link	c.3944+8761C>T		intron_variant	Intron 14 of 17	1	NM_024513.4	ENSP00000296137.2

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19210

AN:

152088

Hom.:

4086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0512

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.0899

GnomAD2 exomes

AF:

0.0338

AC:

8474

AN:

250474

AF XY:

0.0253

show subpopulations

Gnomad AFR exome

AF:

0.446

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.000979

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00172

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0138

AC:

20118

AN:

1459888

Hom.:

3628

Cov.:

AF XY:

0.0121

AC XY:

8800

AN XY:

725974

show subpopulations

African (AFR)

AF:

0.451

AC:

15083

AN:

33428

American (AMR)

AF:

0.0251

AC:

1121

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00984

AC:

256

AN:

26016

East Asian (EAS)

AF:

0.000429

AC:

AN:

39650

South Asian (SAS)

AF:

0.00303

AC:

261

AN:

86062

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.0229

AC:

132

AN:

5766

European-Non Finnish (NFE)

AF:

0.00130

AC:

1446

AN:

1110570

Other (OTH)

AF:

0.0298

AC:

1800

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

663

1326

1990

2653

3316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.126

AC:

19241

AN:

152206

Hom.:

4086

Cov.:

AF XY:

0.121

AC XY:

9006

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.436

AC:

18069

AN:

41446

American (AMR)

AF:

0.0510

AC:

781

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5188

South Asian (SAS)

AF:

0.00497

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00184

AC:

125

AN:

68024

Other (OTH)

AF:

0.0889

AC:

188

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

553

1106

1660

2213

2766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.114

Hom.:

2871

Bravo

AF:

0.145

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.418

AC:

1842

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.0414

AC:

5028

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

T;T;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.45

.;.;.;T

MetaRNN

Benign

0.00046

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L;L

PhyloP100

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.83

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.68

P;P;P;P

Vest4

0.058

MPC

0.49

ClinPred

0.017

GERP RS

3.8

Varity_R

0.051

gMVP

0.21

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over