3-45947552-T-G

Variant names:

• chr3-45947552-T-G
• rs2234358
• NM_006564.2:c.*42T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006564.2(CXCR6):​c.*42T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,499,736 control chromosomes in the GnomAD database, including 209,726 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19060 hom., cov: 33)
  • Exomes 𝑓: 0.53 (190666 hom.)
• Consequence: CXCR6 NM_006564.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 44 publications found

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006564.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR6	NM_006564.2	MANE Select	c.*42T>G		3_prime_UTR	Exon 2 of 2	NP_006555.1
	FYCO1	NM_024513.4	MANE Select	c.3944+7697A>C		intron	N/A	NP_078789.2
	CXCR6	NM_001386435.1		c.*42T>G		3_prime_UTR	Exon 2 of 2	NP_001373364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR6	ENST00000304552.5	TSL:1 MANE Select	c.*42T>G		3_prime_UTR	Exon 2 of 2	ENSP00000304414.4
	FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.3944+7697A>C		intron	N/A	ENSP00000296137.2
	CXCR6	ENST00000438735.1	TSL:3	c.*42T>G		3_prime_UTR	Exon 2 of 2	ENSP00000396218.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73851 AN: 152000 Hom.: 19041 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.497

GnomAD2 exomes AF: 0.568 AC: 136644 AN: 240712 AF XY: 0.571

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.681

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.662

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.512

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.527 AC: 709569 AN: 1347618 Hom.: 190666 Cov.: 20 AF XY: 0.532 AC XY: 358163 AN XY: 673448

African (AFR) AF: 0.329 AC: 10184 AN: 30974

American (AMR) AF: 0.671 AC: 29225 AN: 43582

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 14314 AN: 24492

East Asian (EAS) AF: 0.625 AC: 24359 AN: 38976

South Asian (SAS) AF: 0.698 AC: 57010 AN: 81704

European-Finnish (FIN) AF: 0.574 AC: 30238 AN: 52718

Middle Eastern (MID) AF: 0.566 AC: 3089 AN: 5460

European-Non Finnish (NFE) AF: 0.504 AC: 510480 AN: 1013326

Other (OTH) AF: 0.544 AC: 30670 AN: 56386

GnomAD4 genome AF: 0.486 AC: 73904 AN: 152118 Hom.: 19060 Cov.: 33 AF XY: 0.497 AC XY: 36959 AN XY: 74360

African (AFR) AF: 0.330 AC: 13701 AN: 41512

American (AMR) AF: 0.599 AC: 9159 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2046 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3437 AN: 5166

South Asian (SAS) AF: 0.715 AC: 3441 AN: 4814

European-Finnish (FIN) AF: 0.581 AC: 6145 AN: 10572

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34221 AN: 67978

Other (OTH) AF: 0.503 AC: 1065 AN: 2116

Alfa AF: 0.504 Hom.: 86099

Bravo AF: 0.473

Asia WGS AF: 0.705 AC: 2450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2234358; hg19: chr3-45989044;