chr3-45896597-T-G

Variant names:

• chr3-45896597-T-G
• rs1488371
• NM_031200.3:c.21+1643T>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.21+1643T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,056 control chromosomes in the GnomAD database, including 23,302 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 0.51 (23302 hom., cov: 31)
• Consequence: CCR9 NM_031200.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 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.21+1643T>G		intron	N/A	NP_112477.1
	CCR9	NM_001386447.1		c.21+1643T>G		intron	N/A	NP_001373376.1
	CCR9	NM_001386448.1		c.21+1643T>G		intron	N/A	NP_001373377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR9	ENST00000357632.7	TSL:1 MANE Select	c.21+1643T>G		intron	N/A	ENSP00000350256.2
	CCR9	ENST00000395963.2	TSL:1	c.-15-4213T>G		intron	N/A	ENSP00000379292.2
	CCR9	ENST00000422395.1	TSL:1	c.22-964T>G		intron	N/A	ENSP00000393267.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78146 AN: 151938 Hom.: 23258 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.514 AC: 78231 AN: 152056 Hom.: 23302 Cov.: 31 AF XY: 0.512 AC XY: 38060 AN XY: 74318

African (AFR) AF: 0.824 AC: 34213 AN: 41498

American (AMR) AF: 0.383 AC: 5848 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1628 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1873 AN: 5166

South Asian (SAS) AF: 0.616 AC: 2961 AN: 4808

European-Finnish (FIN) AF: 0.382 AC: 4037 AN: 10570

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26125 AN: 67940

Other (OTH) AF: 0.506 AC: 1071 AN: 2116

Alfa AF: 0.376 Hom.: 1727

Bravo AF: 0.528

Asia WGS AF: 0.476 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		0.84
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: rs1488371; hg19: chr3-45938089;