rs588019

Positions:

• chr17-40558855-G-A
• chr17-40558855-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000246657.2(CCR7):​c.60+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,594,012 control chromosomes in the GnomAD database, including 4,654 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 0.053 (268 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4386 hom.)
• Consequence: CCR7 ENST00000246657.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR7	NM_001838.4	c.60+38C>T		intron_variant		ENST00000246657.2	NP_001829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR7	ENST00000246657.2	c.60+38C>T		intron_variant		1	NM_001838.4	ENSP00000246657	P1
CCR7	ENST00000579344.1	c.42+38C>T		intron_variant		1		ENSP00000462631
CCR7	ENST00000578085.1	c.-129-3037C>T		intron_variant		3		ENSP00000463075

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8141 AN: 152148 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0943

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0656 AC: 16418 AN: 250234 Hom.: 660 AF XY: 0.0685 AC XY: 9265 AN XY: 135238

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.0420

Gnomad ASJ exome AF: 0.0659

Gnomad EAS exome AF: 0.0603

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0527

Gnomad NFE exome AF: 0.0733

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0745 AC: 107438 AN: 1441746 Hom.: 4386 Cov.: 27 AF XY: 0.0751 AC XY: 53949 AN XY: 718526

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0432

Gnomad4 ASJ exome AF: 0.0639

Gnomad4 EAS exome AF: 0.0567

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0540

Gnomad4 NFE exome AF: 0.0778

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0534 AC: 8138 AN: 152266 Hom.: 268 Cov.: 32 AF XY: 0.0540 AC XY: 4018 AN XY: 74452

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0508

Gnomad4 ASJ AF: 0.0654

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.0932

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0486 Hom.: 87

Bravo AF: 0.0485

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs588019; hg19: chr17-38715107;