17-7260947-G-C

Variant names:

• chr17-7260947-G-C
• rs149308129
• NM_001307.6:c.262C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001307.6(CLDN7):​c.262C>G​(p.Leu88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L88L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CLDN7 NM_001307.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838
• Publications: 0 publications found

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]

ENSG00000262302 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31403136).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN7	NM_001307.6	MANE Select	c.262C>G	p.Leu88Val	missense	Exon 2 of 4	NP_001298.3
	CLDN7	NM_001185022.2		c.262C>G	p.Leu88Val	missense	Exon 3 of 5	NP_001171951.1	A0A384ME58
	CLDN7	NM_001185023.2		c.262C>G	p.Leu88Val	missense	Exon 2 of 3	NP_001171952.1	F5H496

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN7	ENST00000360325.11	TSL:1 MANE Select	c.262C>G	p.Leu88Val	missense	Exon 2 of 4	ENSP00000353475.7	O95471-1
	CLDN7	ENST00000397317.8	TSL:1	c.262C>G	p.Leu88Val	missense	Exon 3 of 5	ENSP00000396638.3	O95471-1
	CLDN7	ENST00000574070.5	TSL:1	c.13C>G	p.Leu5Val	missense	Exon 1 of 3	ENSP00000460550.1	I3L3L6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461256 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.77	N
PhyloP100		0.84
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.19
Sift	Benign	0.25	T
Sift4G	Benign	0.56	T
Polyphen		0.69	P
Vest4		0.18
MutPred		0.68		Gain of catalytic residue at L88 (P = 0.0262)
MVP		0.75
MPC		0.51
ClinPred		0.29	T
GERP RS		-1.1
PromoterAI		0.00040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.088
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs149308129; hg19: chr17-7164266;