dbSNP rs12721497: CCR9:p.Met284Val (chr3-45901638-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 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=0.002496183).

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

GnomAD3 exomes

AF:

0.00297

AC:

747

AN:

251452

Hom.:

AF XY:

0.00274

AC XY:

373

AN XY:

135894

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 SAS exome

AF:

0.00447

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

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.0126

Gnomad4 SAS exome

AF:

0.00446

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000399

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.00536

AC:

816

AN:

152338

Hom.:

Cov.:

AF XY:

0.00548

AC XY:

408

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00713

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00179

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

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;.

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over