17-40555417-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001838.4(CCR7):​c.462C>A​(p.Arg154Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,613,972 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 64 hom. )

Consequence

CCR7
NM_001838.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.39
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 Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 17-40555417-G-T is Benign according to our data. Variant chr17-40555417-G-T is described in ClinVar as [Benign]. Clinvar id is 781364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.39 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCR7NM_001838.4 linkc.462C>A p.Arg154Arg synonymous_variant 3/3 ENST00000246657.2 NP_001829.1 P32248A0N0Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCR7ENST00000246657.2 linkc.462C>A p.Arg154Arg synonymous_variant 3/31 NM_001838.4 ENSP00000246657.2 P32248
CCR7ENST00000579344.1 linkc.444C>A p.Arg148Arg synonymous_variant 3/31 ENSP00000462631.1 J3KSS9
CCR7ENST00000578085.1 linkc.273C>A p.Arg91Arg synonymous_variant 2/23 ENSP00000463075.1 J3KTN5

Frequencies

GnomAD3 genomes
AF:
0.0173
AC:
2630
AN:
152174
Hom.:
68
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0592
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00746
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.0187
GnomAD3 exomes
AF:
0.00457
AC:
1146
AN:
250972
Hom.:
29
AF XY:
0.00342
AC XY:
464
AN XY:
135666
show subpopulations
Gnomad AFR exome
AF:
0.0578
Gnomad AMR exome
AF:
0.00390
Gnomad ASJ exome
AF:
0.000894
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000335
Gnomad OTH exome
AF:
0.00277
GnomAD4 exome
AF:
0.00187
AC:
2733
AN:
1461680
Hom.:
64
Cov.:
32
AF XY:
0.00163
AC XY:
1184
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.0582
Gnomad4 AMR exome
AF:
0.00479
Gnomad4 ASJ exome
AF:
0.000689
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000241
Gnomad4 OTH exome
AF:
0.00406
GnomAD4 genome
AF:
0.0173
AC:
2634
AN:
152292
Hom.:
68
Cov.:
32
AF XY:
0.0168
AC XY:
1250
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0591
Gnomad4 AMR
AF:
0.00745
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.0185
Alfa
AF:
0.0113
Hom.:
19
Bravo
AF:
0.0207
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000474

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 12, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
8.8
DANN
Benign
0.57

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: rs2002724; hg19: chr17-38711669; API