17-40563547-C-T

Variant names:

• chr17-40563547-C-T
• rs3136685
• NM_001838.4:c.10+1853G>A

Variant summary

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

The NM_001838.4(CCR7):​c.10+1853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,958 control chromosomes in the GnomAD database, including 6,622 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 0.26 (6622 hom., cov: 31)
• Consequence: CCR7 NM_001838.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 24 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR7	NM_001838.4	c.10+1853G>A		intron_variant	Intron 1 of 2	ENST00000246657.2	NP_001829.1
CCR7	NM_001301714.2	c.-130+1853G>A		intron_variant	Intron 1 of 1		NP_001288643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR7	ENST00000246657.2	c.10+1853G>A		intron_variant	Intron 1 of 2	1	NM_001838.4	ENSP00000246657.2
CCR7	ENST00000578085.1	c.-130+1853G>A		intron_variant	Intron 1 of 1	3		ENSP00000463075.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39558 AN: 151840 Hom.: 6584 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39641 AN: 151958 Hom.: 6622 Cov.: 31 AF XY: 0.261 AC XY: 19355 AN XY: 74274

African (AFR) AF: 0.471 AC: 19457 AN: 41348

American (AMR) AF: 0.208 AC: 3183 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3466

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5172

South Asian (SAS) AF: 0.212 AC: 1024 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1701 AN: 10578

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11076 AN: 67978

Other (OTH) AF: 0.247 AC: 521 AN: 2106

Alfa AF: 0.191 Hom.: 5397

Bravo AF: 0.277

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	14
DANN	Benign	0.72
PhyloP100		1.3
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: rs3136685; hg19: chr17-38719799;