17-40555370-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001838.4(CCR7):​c.509G>A​(p.Arg170His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

CCR7
NM_001838.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
Variant links:
Genes affected
CCR7 (HGNC:1608): (C-C motif chemokine receptor 7) The protein encoded by this gene is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. It has been shown to control the migration of memory T cells to inflamed tissues, as well as stimulate dendritic cell maturation. The chemokine (C-C motif) ligand 19 (CCL19/ECL) has been reported to be a specific ligand of this receptor. Signals mediated by this receptor regulate T cell homeostasis in lymph nodes, and may also function in the activation and polarization of T cells, and in chronic inflammation pathogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34086627).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCR7NM_001838.4 linkc.509G>A p.Arg170His missense_variant Exon 3 of 3 ENST00000246657.2 NP_001829.1 P32248A0N0Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCR7ENST00000246657.2 linkc.509G>A p.Arg170His missense_variant Exon 3 of 3 1 NM_001838.4 ENSP00000246657.2 P32248
CCR7ENST00000579344.1 linkc.491G>A p.Arg164His missense_variant Exon 3 of 3 1 ENSP00000462631.1 J3KSS9
CCR7ENST00000578085.1 linkc.320G>A p.Arg107His missense_variant Exon 2 of 2 3 ENSP00000463075.1 J3KTN5

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
251232
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000968
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000265
AC:
388
AN:
1461824
Hom.:
0
Cov.:
32
AF XY:
0.000263
AC XY:
191
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000343
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000213
Hom.:
0
Bravo
AF:
0.0000869
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.509G>A (p.R170H) alteration is located in exon 3 (coding exon 3) of the CCR7 gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a histidine (H). 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
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.37
T;.;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Benign
0.61
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.34
T;T;T
MetaSVM
Benign
-0.48
T
MutationAssessor
Pathogenic
3.0
M;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.6
D;.;.
REVEL
Benign
0.24
Sift
Uncertain
0.0070
D;.;.
Sift4G
Uncertain
0.030
D;D;.
Polyphen
1.0
D;.;.
Vest4
0.34
MVP
0.52
MPC
1.8
ClinPred
0.58
D
GERP RS
5.2
Varity_R
0.42
gMVP
0.33

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.

Other links and lift over

dbSNP: rs374373475; hg19: chr17-38711622; API