3-45901638-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031200.3(CCR9):c.850A>G(p.Met284Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,614,184 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.0054 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 12 hom. )

Consequence

CCR9
NM_031200.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.438

Publications

15 publications found

Variant links:

Genes affected

CCR9 (HGNC:1610): (C-C motif chemokine receptor 9) The protein encoded by this gene is a G protein-coupled receptor with seven transmembrane domains that belongs to the beta chemokine receptor family. Chemokines and their receptors are key regulators of thymocyte migration and maturation in normal and inflammation conditions. This gene is differentially expressed in T lymphocytes of the small intestine and colon, and its interaction with chemokine 25 contributes to intestinal intra-epithelial lymphocyte homing to the small intestine. This suggests a role for this gene in directing immune responses to different segments of the gastrointestinal tract. This gene and its exclusive ligand, chemokine 25, are overexpressed in a variety of malignant tumors and are closely associated with tumor proliferation, apoptosis, invasion, migration and drug resistance. This gene maps to the chemokine receptor gene cluster. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

CCR9 links:

LZTFL1 (HGNC:6741): (leucine zipper transcription factor like 1) This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. [provided by RefSeq, Aug 2020]

LZTFL1 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Bardet-Biedl syndrome 17
Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LZTFL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002496183).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR9	NM_031200.3 link	c.850A>G	p.Met284Val	missense_variant	Exon 3 of 3	ENST00000357632.7	NP_112477.1	P51686-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR9	ENST00000357632.7 link	c.850A>G	p.Met284Val	missense_variant	Exon 3 of 3	1	NM_031200.3	ENSP00000350256.2		P51686-1

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

817

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00712

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00297

AC:

747

AN:

251452

AF XY:

0.00274

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00680

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000756

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00150

AC:

2186

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

1128

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0146

AC:

490

AN:

33478

American (AMR)

AF:

0.00215

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00241

AC:

AN:

26136

East Asian (EAS)

AF:

0.0126

AC:

500

AN:

39696

South Asian (SAS)

AF:

0.00446

AC:

385

AN:

86256

European-Finnish (FIN)

AF:

0.000243

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000399

AC:

444

AN:

1111974

Other (OTH)

AF:

0.00267

AC:

161

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00536

AC:

816

AN:

152338

Hom.:

Cov.:

AF XY:

0.00548

AC XY:

408

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0158

AC:

656

AN:

41564

American (AMR)

AF:

0.00235

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00713

AC:

AN:

5186

South Asian (SAS)

AF:

0.00373

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68034

Other (OTH)

AF:

0.00756

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00212

Hom.:

Bravo

AF:

0.00616

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0170

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00352

AC:

428

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.000830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.059

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.056

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.49

T;T;.

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.89

.;N;.

PhyloP100

-0.44

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.67

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.59

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0020

.;B;.

Vest4

0.079

MVP

0.48

MPC

0.31

ClinPred

0.00026

GERP RS

-4.8

Varity_R

0.13

gMVP

0.24

Mutation Taster

=91/9

polymorphism

(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

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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