chr17-40557434-G-A

Position:

• chr17-40557434-G-A

Variant summary

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

The NM_001838.4(CCR7):​c.60+1459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,226 control chromosomes in the GnomAD database, including 52,679 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 0.83 (52679 hom., cov: 33)
• Consequence: CCR7 NM_001838.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR7	NM_001838.4	c.60+1459C>T		intron_variant		ENST00000246657.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR7	ENST00000246657.2	c.60+1459C>T		intron_variant		1	NM_001838.4	P1
CCR7	ENST00000579344.1	c.42+1459C>T		intron_variant		1
CCR7	ENST00000578085.1	c.-129-1616C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125704 AN: 152110 Hom.: 52621 Cov.: 33

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.827 AC: 125823 AN: 152226 Hom.: 52679 Cov.: 33 AF XY: 0.830 AC XY: 61739 AN XY: 74418

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.830

Alfa AF: 0.767 Hom.: 60892

Bravo AF: 0.839

Asia WGS AF: 0.891 AC: 3099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs2023906; hg19: chr17-38713686;