17-7260941-G-C

Variant names:

• chr17-7260941-G-C
• rs750701862
• NM_001307.6:c.268C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001307.6(CLDN7):​c.268C>G​(p.Leu90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CLDN7 NM_001307.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.555
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12504995).

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.268C>G	p.Leu90Val	missense	Exon 2 of 4	NP_001298.3
	CLDN7	NM_001185022.2		c.268C>G	p.Leu90Val	missense	Exon 3 of 5	NP_001171951.1	A0A384ME58
	CLDN7	NM_001185023.2		c.268C>G	p.Leu90Val	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.268C>G	p.Leu90Val	missense	Exon 2 of 4	ENSP00000353475.7	O95471-1
	CLDN7	ENST00000397317.8	TSL:1	c.268C>G	p.Leu90Val	missense	Exon 3 of 5	ENSP00000396638.3	O95471-1
	CLDN7	ENST00000574070.5	TSL:1	c.19C>G	p.Leu7Val	missense	Exon 1 of 3	ENSP00000460550.1	I3L3L6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250604 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461386 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727064

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52984

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111970

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.13	T
PhyloP100		-0.56
Sift4G	Uncertain	0.030	D
Vest4		0.21
MVP		0.61
ClinPred		0.061	T
GERP RS		1.4
PromoterAI		-0.092	Neutral
Varity_R		0.11
Mutation Taster		=66/34	polymorphism

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: rs750701862; hg19: chr17-7164260;