3-45902103-C-G

Position:

• chr3-45902103-C-G

Variant summary

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

The NM_031200.3(CCR9):​c.*205C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.09 in 526,028 control chromosomes in the GnomAD database, including 2,631 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 0.079 (616 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2015 hom.)
• Consequence: CCR9 NM_031200.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.876

Genes affected

CCR9 (HGNC:1610): (C-C motif chemokine receptor 9) The protein encoded by this gene is a G protein-coupled receptor with seven transmembrane domains that belongs to the beta chemokine receptor family. Chemokines and their receptors are key regulators of thymocyte migration and maturation in normal and inflammation conditions. This gene is differentially expressed in T lymphocytes of the small intestine and colon, and its interaction with chemokine 25 contributes to intestinal intra-epithelial lymphocyte homing to the small intestine. This suggests a role for this gene in directing immune responses to different segments of the gastrointestinal tract. This gene and its exclusive ligand, chemokine 25, are overexpressed in a variety of malignant tumors and are closely associated with tumor proliferation, apoptosis, invasion, migration and drug resistance. This gene maps to the chemokine receptor gene cluster. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

LZTFL1 (HGNC:6741): (leucine zipper transcription factor like 1) This gene encodes a ubiquitously expressed protein that localizes to the cytoplasm. This protein interacts with Bardet-Biedl Syndrome (BBS) proteins and, through its interaction with BBS protein complexes, regulates protein trafficking to the ciliary membrane. Nonsense mutations in this gene cause a form of Bardet-Biedl Syndrome; a ciliopathy characterized in part by polydactyly, obesity, cognitive impairment, hypogonadism, and kidney failure. This gene may also function as a tumor suppressor; possibly by interacting with E-cadherin and the actin cytoskeleton and thereby regulating the transition of epithelial cells to mesenchymal cells. [provided by RefSeq, Aug 2020]

LZTFL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR9	NM_031200.3	c.*205C>G		3_prime_UTR_variant	3/3	ENST00000357632.7	NP_112477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR9	ENST00000357632.7	c.*205C>G		3_prime_UTR_variant	3/3	1	NM_031200.3	ENSP00000350256.2

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12024 AN: 152170 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0622

GnomAD4 exome AF: 0.0946 AC: 35341 AN: 373740 Hom.: 2015 Cov.: 4 AF XY: 0.0922 AC XY: 17729 AN XY: 192344

Gnomad4 AFR exome AF: 0.0213

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0000374

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.0855

GnomAD4 genome AF: 0.0790 AC: 12026 AN: 152288 Hom.: 616 Cov.: 32 AF XY: 0.0787 AC XY: 5861 AN XY: 74442

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0676

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0977 Hom.: 111

Bravo AF: 0.0709

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.64

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: rs17765088; hg19: chr3-45943595;