dbSNP rs222857: CLDN7:c.224-259G>T (chr17-7261244-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001307.6(CLDN7):c.224-259G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLDN7
NM_001307.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.193

Publications

38 publications found

Variant links:

Genes affected

CLDN7 (HGNC:2049): (claudin 7) This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. Differential expression of this gene has been observed in different types of malignancies, including breast cancer, ovarian cancer, hepatocellular carcinomas, urinary tumors, prostate cancer, lung cancer, head and neck cancers, thyroid carcinomas, etc.. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

CLDN7 links:

ENSG00000262302 (HGNC:):

ENSG00000262302 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001307.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLDN7	NM_001307.6	MANE Select	c.224-259G>T	intron	N/A	NP_001298.3
CLDN7	NM_001185022.2		c.224-259G>T	intron	N/A	NP_001171951.1	A0A384ME58
CLDN7	NM_001185023.2		c.224-259G>T	intron	N/A	NP_001171952.1	F5H496

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLDN7	ENST00000360325.11	TSL:1 MANE Select	c.224-259G>T	intron	N/A	ENSP00000353475.7	O95471-1
CLDN7	ENST00000397317.8	TSL:1	c.224-259G>T	intron	N/A	ENSP00000396638.3	O95471-1
ENSG00000262302	ENST00000577138.1	TSL:3	n.223+577G>T	intron	N/A	ENSP00000460571.1	I3L3M4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

393740

Hom.:

AF XY:

0.00

AC XY:

AN XY:

208234

African (AFR)

AF:

0.00

AC:

AN:

9798

American (AMR)

AF:

0.00

AC:

AN:

15348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11702

East Asian (EAS)

AF:

0.00

AC:

AN:

25338

South Asian (SAS)

AF:

0.00

AC:

AN:

43198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

238612

Other (OTH)

AF:

0.00

AC:

AN:

22676

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.19

PromoterAI

-0.22

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.92

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.92

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over