3-45902103-C-G

Variant names:

• chr3-45902103-C-G
• rs17765088
• NM_031200.3:c.*205C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bardet-Biedl syndrome 17

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031200.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR9	NM_031200.3	MANE Select	c.*205C>G		3_prime_UTR	Exon 3 of 3	NP_112477.1
	CCR9	NM_001386447.1		c.*205C>G		3_prime_UTR	Exon 3 of 3	NP_001373376.1
	CCR9	NM_001386448.1		c.*205C>G		3_prime_UTR	Exon 3 of 3	NP_001373377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR9	ENST00000357632.7	TSL:1 MANE Select	c.*205C>G		3_prime_UTR	Exon 3 of 3	ENSP00000350256.2
	CCR9	ENST00000395963.2	TSL:1	c.*205C>G		3_prime_UTR	Exon 2 of 2	ENSP00000379292.2
	CCR9	ENST00000902118.1		c.*205C>G		3_prime_UTR	Exon 3 of 3	ENSP00000572177.1

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

African (AFR) AF: 0.0213 AC: 225 AN: 10588

American (AMR) AF: 0.0718 AC: 873 AN: 12152

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 1438 AN: 11738

East Asian (EAS) AF: 0.0000374 AC: 1 AN: 26750

South Asian (SAS) AF: 0.0193 AC: 474 AN: 24602

European-Finnish (FIN) AF: 0.142 AC: 5439 AN: 38432

Middle Eastern (MID) AF: 0.0209 AC: 35 AN: 1676

European-Non Finnish (NFE) AF: 0.111 AC: 25008 AN: 226190

Other (OTH) AF: 0.0855 AC: 1848 AN: 21612

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

African (AFR) AF: 0.0222 AC: 924 AN: 41582

American (AMR) AF: 0.0676 AC: 1035 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 421 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4826

European-Finnish (FIN) AF: 0.148 AC: 1565 AN: 10584

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7679 AN: 68022

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		0.88
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: rs17765088; hg19: chr3-45943595;